The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
ATM Mutations in Patients with Hereditary Pancreatic Cancer
Open accessPublished version of a preprint
Abstract
Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. Significance: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes. Cancer Discovery; 2(1): 41–6. ©2011 AACR. Read the Commentary on this article by Bakker and de Winter, p. 14 This article is highlighted in the In This Issue feature, p. 1
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Pancreatic surveillance is recommended for carriers of germline deleterious variants in cancer susceptibility gene,22–26: BRCA2, ATM, BRCA1, PALB2, CDKN2A, STK11, MLH1 and MSH2.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
SEER Cancer Statistics Review, 1975-2003
Ries, L. A. G., Harkins, D., Krapcho, M. F., Mariotto, A. B., Miller, B., Feuer, E. J., Clegg, L. X., Eisner, M. P., Horner, M., Howlader, N., et al. (2006) · Digital Archive @ GSU · Cited by 11,404
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161
Self-citationJiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., et al. (2011) · Science · doi:10.1126/science.1200609 · Cited by 1,744
Self-citationAtaxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
Lavin, M. F. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2514 · Cited by 901
The Human Gene Mutation Database: 2008 update
Stenson, P. D., Mort, M., Ball, E. V., Howells, K., Phillips, A. D., Thomas, N. S., & Cooper, D. N. (2009) · Genome Medicine · doi:10.1186/gm13 · Cited by 873
Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene
Jones, S., Hruban, R. H., Kamiyama, M., Borges, M., Zhang, X., Parsons, D. W., Lin, J. C.-H., Palmisano, E., Brune, K., Jaffee, E. M., et al. (2009) · Science · doi:10.1126/science.1171202 · Cited by 826 · cited 1×
“Unbiased, genome-wide sequencing can be used to identify familial pancreatic genes, as demonstrated by the finding that PALB2 is a pancreatic cancer susceptibility gene (3).”
BackgroundSelf-citationBreast and Other Cancers in Families with Ataxia-Telangiectasia
Swift, M., Reitnauer, P. J., Morrell, D., & Chase, C. L. (1987) · New England Journal of Medicine · doi:10.1056/nejm198705213162101 · Cited by 717
The human gene mutation database
Cooper, D. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.285 · Cited by 604
Flagged first, then by citations
1 of the 30 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–200 of 492
Genetics and Biology of Pancreatic Ductal Adenocarcinoma
Dunne, R. F., & Hezel, A. F. (2015) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2015.04.003 · Cited by 68
Germline genetic variability in pancreatic cancer risk and prognosis
Gentiluomo, M., Canzian, F., Nicolini, A., Gemignani, F., Landi, S., & Campa, D. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.08.003 · Cited by 68
Dunlop, C. R., Wallez, Y., Johnson, T. I., Fernández, S. B. D. Q., Durant, S. T., Cadogan, E. B., Lau, A., Richards, F. M., & Jodrell, D. I. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-1016-2 · Cited by 64
Clinical and pathologic features of familial pancreatic cancer
Humphris, J. L., Johns, A. L., Simpson, S. H., Cowley, M. J., Pajic, M., Chang, D. K.-F., Nagrial, A. M., Chin, V. T., Chantrill, L. A., Pinese, M., et al. (2014) · Cancer · doi:10.1002/cncr.28863 · Cited by 65
Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care
Graffeo, R., Livraghi, L., Pagani, O., Goldhirsch, A., Partridge, A. H., & Garber, J. E. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-4003-9 · Cited by 69
Current Approaches to Pancreatic Cancer Screening
Chhoda, A., Lu, L., Clerkin, B. M., Risch, H. A., & Farrell, J. J. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.09.013 · Cited by 64
“It is an autosomal recessive disorder, characterized by progressive neurologic abnormalities along with immune dysfunction and predisposition to lymphoma and leukemia, resulting from hypersensitivity to ionizing radiation.(25) Monoallelic mutation in the ATM gene results in increased risk of breast cancer and doubled…”
BackgroundSkaro, M. F., Nanda, N., Gauthier, C. D., Felsenstein, M., Jiang, Z., Qiu, M., Shindo, K., Yu, J., Hutchings, D., Javed, A. A., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.01.254 · Cited by 65
Self-citationNeoplasms of the Exocrine Pancreas
Wolff, R. A., Crane, C. H., Li, D., Evans, D. B., Maitra, A., & Tsai, S. (2017) · Wiley eBooks · doi:10.1002/9781119000822.hfcm094 · Cited by 64
Diagnostic Cancer Genome Sequencing and the Contribution of Germline Variants
Kilpivaara, O., & Aaltonen, L. A. (2013) · Science · doi:10.1126/science.1233899 · Cited by 61
Zhang, C., Jiang, F., Su, C., Xie, P., & Xu, L. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28444 · Cited by 63
Klatte, D. C. F., Wallace, M. B., Löhr, M. J., Bruno, M. J., & van Leerdam, M. E. (2022) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2021.101783 · Cited by 68
Chang, D. K.-F., Grimmond, S. M., & Biankin, A. V. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.12.001 · Cited by 62
Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility
de Voer, R. M., Hahn, M., Weren, R. D. A., Mensenkamp, A. R., Gilissen, C., van Zelst-Stams, W. A., Spruijt, L., Kets, C. M., Zhang, J., Venselaar, H., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005880 · Cited by 64
Loss of DNA Damage Response in Neuroblastoma and Utility of a PARP Inhibitor
Takagi, M., Yoshida, M., Nemoto, Y., Tamaichi, H., Tsuchida, R., Seki, M., Uryu, K., Hoshino, N., Nishii, R., Miyamoto, S., et al. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx062 · Cited by 63
“For example, rare ATM SNVs confer strong cancer predisposition in familial pancreatic cancer; however, familial pancreatic cancer with ATM SNVs is relatively rare (47,48).”
BackgroundHacking Pancreatic Cancer: Present and Future of Personalized Medicine
Federico, A. D., Tateo, V., Parisi, C., Formica, F., Carloni, R., Frega, G., Rizzo, A., Ricci, D., Marco, M. D., Palloni, A., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14070677 · Cited by 61
Hong, S., Vincent, A., Kanda, M., Leclerc, J., Omura, N., Borges, M. W., Klein, A. P., Canto, M. I., Hruban, R. H., & Goggins, M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1075 · Cited by 59
Self-citationMultigene Hereditary Cancer Panels Reveal High-Risk Pancreatic Cancer Susceptibility Genes
Hu, C., LaDuca, H., Shimelis, H., Polley, E. C., Lilyquist, J., Hart, S. N., Na, J., Thomas, A., Lee, K. Y., Davis, B. T., et al. (2018) · JCO Precision Oncology · doi:10.1200/po.17.00291 · Cited by 57
“of Patients Testeda Genes Included BRCAplus (6) 25 BRCA1, BRCA2, CDH1, PTEN, PALB2,b STK11,c TP53 BreastNext (18) 51 ATM, BARD1, BRCA1,d BRCA2,d BRIP1, CDH1, CHEK2, MRE11A, MUTYH, NBN, NF1,e PALB2, PTEN, RAD50, RAD51C, RAD51D,e STK11,c TP53 ColoNext (17) 19 APC, BMPR1A, CDH1, CHEK2, EPCAM,f GREM1,fg MLH1, MSH2, MSH6,…”
Familial and sporadic pancreatic cancer share the same molecular pathogenesis
Norris, A. L., Roberts, N. J., Jones, S., Wheelan, S. J., Papadopoulos, N., Vogelstein, B., Kinzler, K. W., Hruban, R. H., Klein, A. P., & Eshleman, J. R. (2014) · Familial Cancer · doi:10.1007/s10689-014-9755-y · Cited by 57
Self-citationMolecular pathology of pancreatic cancer
Saiki, Y., & Horii, A. (2014) · Pathology International · doi:10.1111/pin.12114 · Cited by 58
Pancreatic cancer screening in high-risk individuals with germline genetic mutations
Davee, T. R., Coronel, E. S., Papafragkakis, C., Thaiudom, S., Lanke, G., Chakinala, R. C., Nogueras‐González, G. M., Bhutani, M. S., Ross, W. A., Weston, B. R., et al. (2018) · Gastrointestinal Endoscopy · doi:10.1016/j.gie.2017.12.019 · Cited by 56
Ohmoto, A., Yachida, S., & Morizane, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030561 · Cited by 58
“4%) FPC probands in comparison with no mutation in a control cohort [53].”
BackgroundBazzichetto, C., Luchini, C., Conciatori, F., Vaccaro, V., Cello, I. D., Mattiolo, P., Falcone, I., Ferretti, G., Scarpa, A., Cognetti, F., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228841 · Cited by 58
“Consistently, patients affected by ataxia telangiectasia, a severe syndrome due to biallelic mutations in ATM, display increased susceptibility to different types of cancer, including hereditary pancreatic cancer [65].”
BackgroundFamilial pancreatic adenocarcinoma
Petersen, G. M. (2015) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2015.04.007 · Cited by 53
Self-citationTranscriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A
Hoskins, J. W., Jia, J., Flández, M., Parikh, H. M., Xiao, W., Collins, I. J., Emmanuel, M. A., Ibrahim, A. M., Powell, J. I., Zhang, L., et al. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu193 · Cited by 54
“The only sample showing up-regulation of HNF1A was the pancreatic cancer cell line with the least significant dysregulation of the HNF1A sub-network (AsPC1, see Table 2); this cell line showed the highest levels of HNF1A Samples Rank P Rank P Rank P Rank P Rank P All tumor tissues 2 1.92 × 10−5 6 5.42 × 10−5 22 1.11 ×…”
BackgroundInfluentialSelf-citationValero, V., Saunders, T., He, J. P., Weiss, M. J., Cameron, J. L., Dholakia, A. S., Wild, A. T., Shin, E. J., Khashab, M. A., Lennon, A. M., et al. (2015) · Annals of Surgery · doi:10.1097/sla.0000000000001156 · Cited by 55
Self-citationNew Developments in the Molecular Mechanisms of Pancreatic Tumorigenesis
Felsenstein, M., Hruban, R. H., & Wood, L. D. (2017) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000172 · Cited by 59
Self-citationSmith, A. L., Alirezaie, N., Connor, A. A., Chan‐Seng‐Yue, M., Grant, R. C., Selander, I., Bascuñana, C., Borgida, A., Hall, A., Whelan, T., et al. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.10.030 · Cited by 54
Self-citationŞahin, İ. H., Lowery, M. A., Stadler, Z. K., Salo‐Mullen, E. E., Iacobuzio–Donahue, C. A., Kelsen, D. P., & O'Reilly, E. M. (2016) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2016.1153424 · Cited by 56
Yamamoto, K., Wang, J., Sprinzen, L., Xu, J., Haddock, C. J., Li, C., Lee, B. J., Loredan, D. G., Jiang, W., Vindigni, A., et al. (2016) · eLife · doi:10.7554/elife.14709 · Cited by 53
“Recent sequencing studies also identified recurrent ATM mutations in 2–8% of breast, pancreas or gastric cancers (Roberts et al., 2012; Cremona and Behrens, 2014).”
BackgroundInfluentialAbe, K., Kitago, M., Kitagawa, Y., & Hirasawa, A. (2021) · International Journal of Clinical Oncology · doi:10.1007/s10147-021-02015-6 · Cited by 62
Diabetes Type 2 and Pancreatic Cancer: A History Unfolding.
Souza, A. O., Irfan, K., Masud, F., & Saif, M. W. (2016) · PubMed · Cited by 51
Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer
Fostira, F., Saloustros, E. S., Apostolou, P., Vagena, A., Kalfakakou, D., Mauri, D., Tryfonopoulos, D. J., Georgoulias, V., Yannoukakos, D., Fountzilas, G., et al. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4661-x · Cited by 52
“Heterozygous ATM mutations have been associated with two- to fourfold increased risk for FBC [26, 27], while they also seem to increase pancreatic [28] and, possibly, ovarian cancer risk [29].”
BackgroundBarili, V., Ambrosini, E., Bortesi, B., Minari, R., Sensi, E. D., Cannizzaro, I. R., Taiani, A., Michiara, M., Sikokis, A., Boggiani, D., et al. (2024) · Genes · doi:10.3390/genes15020219 · Cited by 56
Risk Factors and Therapeutic Targets in Pancreatic Cancer
Wörmann, S. M., & Algül, H. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00282 · Cited by 51
“4% (4/166) of familial pancreatic cases could be explained by deleterious ataxiatelangiectasia (ATM ) mutations (89).”
BackgroundDrosos, Y., Escobar, D., Chiang, M.-Y., Roys, K., Valentine, V. A., Valentine, M. B., Rehg, J. E., Sahai, V., Begley, L., Ye, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11661-8 · Cited by 51
Germline mutations in pancreatic cancer and potential new therapeutic options
Pihlak, R., Valle, J. W., & McNamara, M. G. (2017) · Oncotarget · doi:10.18632/oncotarget.17291 · Cited by 48
“Depending on family history the BRCA1/2 mutation rates vary between 5–10% [33, 52] and ATM mutations in the same range [53, 54], while CDKN2A mutation levels range from half of that to 3 times higher depending on the depth of sequencing [35, 51], and TP53 mutations are identified in up to 3 out of 4 patients [51].”
BackgroundInfluentialRare germline variants in known melanoma susceptibility genes in familial melanoma
Goldstein, A. M., Xiao, Y., Sampson, J. N., Zhu, B., Rotunno, M., Bennett, H. R., Wen, Y., Jones, K. M., Vogt, A. L., Burdette, L. A., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx368 · Cited by 48
Germline Variants and Risk for Pancreatic Cancer
Zhan, W., Shelton, C. A., Greer, P. J., Brand, R. E., & Whitcomb, D. C. (2018) · Pancreas · doi:10.1097/mpa.0000000000001136 · Cited by 50
Maynard, H., Stadler, Z. K., Berger, M. F., Solit, D. B., Ly, M., Lowery, M. A., Mandelker, D. L., Zhang, L., Jordan, E., Dika, I. E., et al. (2020) · Cancer · doi:10.1002/cncr.32740 · Cited by 48
“2000 Cancer May 1, 2020 gene,(23) more recently, germline mutations in ATM have also been found in individuals with pancreatic cancer.(24)”
BackgroundFamilial Pancreatic Cancer: Current Perspectives
Llach, J., Carballal, S., & Moreira, L. (2020) · Cancer Management and Research · doi:10.2147/cmar.s172421 · Cited by 51
“Other Hereditary Syndromes Li-Fraumeni syndrome (LFS; TP53 gene-), Ataxia telangiectasia (AT; ATM gene) or Cystic fibrosis (CF; CFTR gene) are other syndromes associated with PC with lower cumulative risk (<5%).(35,36) Among these entities, evidence relating germline mutations in ATM with and a high risk of PC is incr…”
BackgroundPanGen-Fam: Spanish registry of hereditary pancreatic cancer
Mocci, E., Guillén‐Ponce, C., Earl, J., Márquez, M., Solera, J., Salazar-Lopez, M.-T., Calcedo-Arnáiz, C., Vázquez-Sequeiros, E., Montáns, J., Beltrán, M. M., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.07.004 · Cited by 47
“At present few 3 genes, all involved in DNA repair, have been identified as responsible for FPC; however germline mutations in these genes explain only 25% of the cases: BRCA2 (15–17%) [7,8], PALB2 (3%) [9–11].”
BackgroundBartsch, D. K., Dietzel, K., Bargello, M., Matthaei, E., Kloeppel, G., Esposito, I., Heverhagen, J. T., Gress, T. M., Slater, E. P., & Langer, P. (2012) · Familial Cancer · doi:10.1007/s10689-012-9582-y · Cited by 47
Inherited mutations in DNA repair genes and cancer risk
Romero-Laorden, N., & Castro, E. (2017) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2017.02.009 · Cited by 47
Genetic Alterations of Periampullary and Pancreatic Ductal Adenocarcinoma: An Overview
Sikdar, N., Saha, G., Dutta, A., Ghosh, S., Shrikhande, S. V., & Banerjee, S. (2018) · Current Genomics · doi:10.2174/1389202919666180221160753 · Cited by 51
“Whole genome analysis of nearly 170 families with FPC revealed heterozygous germline mutation of the ATM gene, in two kindreds with FPC and four families had deleterious homozygous ATM mutations [96].”
BackgroundInfluentialHereditary breast cancer syndromes and genetic testing
Rich, T. A., Woodson, A., Litton, J. K., & Arun, B. K. (2014) · Journal of Surgical Oncology · doi:10.1002/jso.23791 · Cited by 48
“Stomach, ovarian, bladder, and colon cancer risks may also be increased, though the evidence of a strong association is less compelling [189,192].”
BackgroundDNA Sequencing of Cancer: What Have We Learned?
Chmielecki, J., & Meyerson, M. M. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-060712-200152 · Cited by 48
Exome-Wide Association Study of Pancreatic Cancer Risk
Grant, R. C., Denroche, R. E., Borgida, A., Virtanen, C., Cook, N., Smith, A. L., Connor, A. A., Wilson, J. M., Peterson, G., Roberts, N. J., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.10.015 · Cited by 46
Self-citationAdenocarcinoma of the pancreas
Hruban, R. H., & Klimstra, D. S. (2014) · Seminars in Diagnostic Pathology · doi:10.1053/j.semdp.2014.08.004 · Cited by 47
Self-citationNext-Generation Sequencing in Pancreatic Cancer
Shen, G.-Q., Aleassa, E. M., Walsh, R. M., & Morris‐Stiff, G. J. (2019) · Pancreas · doi:10.1097/mpa.0000000000001324 · Cited by 45
“Using different NGS methods, there has been further confirmation that ATM can increase the risk of disease in familial PDAC.(45,48,49) ATM mutations also underlie multiple other cancers including breast, lung, and thyroid cancers, and the identification of an ATM mutation in these cancers should alert to the risk of p…”
MethodPancreatic cancer: molecular pathogenesis and emerging therapeutic strategies
Rozengurt, E., & Eibl, G. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02499-y · Cited by 49
Histamine and histamine receptor regulation of gastrointestinal cancers.
Kennedy, L. L., Hodges, K., Meng, F., Alpini, G. D., & Francis, H. (2012) · PubMed · Cited by 44
Goldstein, J. B., Zhao, L., Wang, X., Ghelman, Y., Overman, M. J., Javle, M. M., Shroff, R. T., Varadhachary, G. R., Wolff, R. A., McAllister, F. M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0224 · Cited by 46
“Clin Cancer Res; 26(6) March 15, 2020 CLINICAL CANCER RESEARCH 1386”
BackgroundInfluentialTesfaye, A. A., Kamgar, M., Azmi, A. S., & Philip, P. A. (2017) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2018.1417844 · Cited by 43
Porter, N. R., Laheru, D. A., Lau, B. M., He, J. P., Zheng, L., Narang, A. K., Roberts, N. J., Canto, M. I., Lennon, A. M., Goggins, M., et al. (2022) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djac167 · Cited by 44
Self-citationATM, radiation, and the risk of second primary breast cancer
Bernstein, J. L., WECARE Study Collaborative Group, & Concannon, P. (2017) · International Journal of Radiation Biology · doi:10.1080/09553002.2017.1344363 · Cited by 41
“in familial gastric and pancreatic cancers (Roberts et al. 2012; Helgason et al. 2015).”
BackgroundAtaxia telangiectasia syndrome: moonlighting ATM
Zaki‐Dizaji, M., Akrami, S. M., Abolhassani, H., Rezaei, N., & Aghamohammadi, A. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1392856 · Cited by 42
“14 ATM is often mutated in a broad range of human cancers, including lung, colorectal, breast, gastric, pancreatic ductal adenocarcinomas and hematopoietic tumors [74, 109, 110, 111, 112].”
BackgroundChen, F., Roberts, N. J., & Klein, A. P. (2017) · Chinese Clinical Oncology · doi:10.21037/cco.2017.12.04 · Cited by 42
Self-citationRare Germline Genetic Variants and the Risks of Epithelial Ovarian Cancer
Pavanello, M., Chan, I. H. Y., Ariff, A., Pharoah, P. D. P., Gayther, S. A., & Ramus, S. J. (2020) · Cancers · doi:10.3390/cancers12103046 · Cited by 44
“ATM is a candidate ovarian cancer susceptibility gene due to its role in breast [67] and pancreatic cancer [68].”
BackgroundDomenico, E. G. D., Romano, E., Porto, P. D., & Ascenzioni, F. (2014) · BioMed Research International · doi:10.1155/2014/787404 · Cited by 39
“ATM heterozygous mutations have been identified by genome-wide sequencing analysis in the germline of nearly 170 patients with history of pancreatic cancer posing ATM as a new potential target gene for predisposition of pancreatic ductal adenocarcinoma [215].”
BackgroundGenomic testing for pancreatic cancer in clinical practice as real-world evidence
Hayashi, H., Tanishima, S., Fujii, K., Mori, R., Okamura, Y., Yanagita, E., Matsuoka, R., Amano, T., Kinoshita, I., Komatsu, Y., et al. (2018) · Pancreatology · doi:10.1016/j.pan.2018.07.006 · Cited by 40
Kasuga, A., Okamoto, T., Udagawa, S., Mori, C., Mie, T., Furukawa, T., Yamada, Y., Takeda, T., Matsuyama, M., Sasaki, T., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031205 · Cited by 41
“Although the lifetime risk for pancreatic cancer remains uncertain, the ATM pathogenic variant is associated with an increased risk of pancreatic cancer [60,61].”
BackgroundJonak, K., Kurpas, M. K., Szołtysek, K., Janus, P., Abramowicz, A., & Puszyński, K. (2016) · BMC Systems Biology · doi:10.1186/s12918-016-0293-0 · Cited by 39
Thompson, E. D., Roberts, N. J., Wood, L. D., Eshleman, J. R., Goggins, M., Kern, S. E., Klein, A. P., & Hruban, R. H. (2020) · Modern Pathology · doi:10.1038/s41379-020-0629-6 · Cited by 41
“These pathogenic germline ATM variants are also present in ~ 2% of unselected patients with pancreatic cancer, indicating that, just as is true for patients with germline pathogenic BRCA gene variants, not all patients with a deleterious germline ATM variant have a family history of cancer [18, 29, 43, 62, 68, 76, 80,…”
BackgroundSelf-citationCannistrà, M., Ruggiero, M., Zullo, A., Serafini, S., Grande, R., & Nardo, B. (2015) · International Journal of Surgery · doi:10.1016/j.ijsu.2015.04.093 · Cited by 38
Pastorino, L., Andreotti, V., Dalmasso, B., Vanni, I., Ciccarese, G., Mandalà, M., Spadola, G., Pizzichetta, M. A., Ponti, G., Tibiletti, M. G., et al. (2020) · Cancers · doi:10.3390/cancers12041007 · Cited by 38
“Conversely, recent exome sequencing studies on PC-only families identified pathogenic variants in the ATM (ataxia-telangiectasia mutated) [32,33] and PALB2 (partner and localizer of BRCA2) genes [34,35].”
BackgroundInherited Rare, Deleterious Variants in ATM Increase Lung Adenocarcinoma Risk
Selvan, M. E., Zauderer, M. G., Rudin, C. M., Jones, S., Mukherjee, S., Offit, K., Onel, K., Rennert, G., Velculescu, V. E., Lipkin, S. M., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.08.017 · Cited by 38
Self-citationEpidemiology and Inherited Predisposition for Sporadic Pancreatic Adenocarcinoma
Stolzenberg‐Solomon, R. Z., & Amundadottir, L. T. (2015) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2015.04.009 · Cited by 37
Grant, R. C., Al-Sukhni, W., Borgida, A., Holter, S., Kanji, Z. S., McPherson, T. A., Whelan, E. R., Serra, S., Trinh, Q. M., Peltekova, V. D., et al. (2013) · Human Genomics · doi:10.1186/1479-7364-7-11 · Cited by 37
“Since the original ES studies [1,2], inactivating PALB2 mutations were found in small proportions of FPC cohorts (for example, Tischkowitz et al.”
BackgroundSelf-citationDudley, B., Karloski, E., Monzon, F. A., Singhi, A. D., Lincoln, S. E., Bahary, N., & Brand, R. E. (2018) · Cancer · doi:10.1002/cncr.31242 · Cited by 39
“Germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, the mismatch repair genes (MLH1, MSH2/EPCAM, MSH6, and PMS2), PALB2, STK11, and TP53 have been associated with an increased risk for PC.(4-12) Historically, individuals with PC have been seldom referred for genetic counseling for several reasons.”
BackgroundUnderstanding pancreatic cancer genomes
Cowley, M. J., Chang, D. K.-F., Pajic, M., Johns, A. L., Waddell, N., Grimmond, S. M., & Biankin, A. V. (2013) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1007/s00534-013-0610-6 · Cited by 36
“ATM was recently implicated as a PDAC susceptibility gene through bi-allelic inactivation in a case of familial PDAC [11].”
BackgroundHereditary Pancreatic Cancer Syndromes
Connor, A. A., & Gallinger, S. (2015) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2015.06.007 · Cited by 36
Self-citationHereditary pancreatic cancer: related syndromes and clinical perspective
Carrera, S., Sancho, A., Azkona, E., Azkuna, J., & López-Vivanco, G. (2017) · Hereditary Cancer in Clinical Practice · doi:10.1186/s13053-017-0069-6 · Cited by 36
“4% (4/166) carried pathogenic ATM variants [92].”
A histomorphologic comparison of familial and sporadic pancreatic cancers
Singhi, A. D., Ishida, H., Ali, S. Z., Goggins, M., Canto, M. I., Wolfgang, C. L., Meriden, Z., Roberts, N. J., Klein, A. P., & Hruban, R. H. (2015) · Pancreatology · doi:10.1016/j.pan.2015.04.003 · Cited by 35
“003 mutations in ATM and PALB2 have been identified as predisposing factors to the development of pancreatic cancer [12,13].”
BackgroundSelf-citationPrincipe, D. R. (2022) · Cancers · doi:10.3390/cancers14040897 · Cited by 38
“For example, ataxia-telangiectasia is associated with an increased risk of PDAC [18].”
BackgroundTuna, M., & Amos, C. I. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.11.004 · Cited by 37
“WGS also facilitates the discovery of cancer predisposition genes and can identify novel rare variants, such as germline mutations in ATM gene were identified in two family with hereditary pancreatic cancer [67].”
BackgroundPARI Overexpression Promotes Genomic Instability and Pancreatic Tumorigenesis
O’Connor, K. W., Dejsuphong, D., Park, E., Nicolae, C. M., Kimmelman, A. C., D’Andrea, A. D., & Moldovan, G. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3313 · Cited by 35
“ATM is a kinase involved in recruiting repair factors to DNA strand breaks (6); ATM mutations have been associated with pancreatic cancer (7, 8).”
BackgroundClinico-genomic Characterization of ATM and HRD in Pancreas Cancer: Application for Practice
Park, W., O'Connor, C. A., Bandlamudi, C., Forman, D., Chou, J. F., Umeda, S., Reyngold, M., Varghese, A. M., Keane, F., Balogun, F., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1483 · Cited by 34
Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer
Williamson, T., de Abreu, M. C., Trembath, D. G., Brayton, C. F., Kang, B., Mendes, T. B., de Assumpção, P. P., Cerutti, J. M., & Riggins, G. J. (2021) · Oncotarget · doi:10.18632/oncotarget.28014 · Cited by 36
The Role of Endoscopic Ultrasonography in the Diagnosis and Staging of Pancreatic Cancer
Zakaria, A., Al-Share, B. A., Klapman, J. B., & Dam, A. N. (2022) · Cancers · doi:10.3390/cancers14061373 · Cited by 34
Epigenetic silencing of EYA2 in pancreatic adenocarcinomas promotes tumor growth
Vincent, A., Hong, S., Hu, C., Omura, N., Young, A., Kim, H., Yu, J., Knight, S., Ayars, M., Griffith, M., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1842 · Cited by 33
“Pancreatic ductal adenocarcinomas develop as a result of clonallyselected genetic events most commonly involving the genes KRAS, CDKN2A, TP53 and SMAD4 [2-6], less commonly ATM and others [3, 5, 7, 8], and for pancreatic ductal adenocarcinomas arising from intraductal”
BackgroundSelf-citationFamilial Pancreatic Cancer and the Future of Directed Screening
Welinsky, S., & Lucas, A. L. (2017) · Gut and Liver · doi:10.5009/gnl16414 · Cited by 33
“Ataxia-telangiectasia (ATM) is an autosomal recessive disorder characterized by progressive neurologic symptoms and resulting in a marked predisposition for cancer, particularly lymphoma and leukemia.(36,37) Monoallelic mutations in the ATM gene, which is involved in DNA repair, confer an increased risk of cancer, par…”
BackgroundEpigenetic Landscape in Pancreatic Ductal Adenocarcinoma: On the Way to Overcoming Drug Resistance?
Čierniková, S., Earl, J., García‐Bermejo, L., Števurková, V., Carrato, A., & Smolková, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114091 · Cited by 36
Abrams, S. L., Lertpiriyapong, K., Yang, L. V., Martelli, A. M., Cocco, L., Ratti, S., Falasca, M., Murata, R. M., Rosalen, P. L., Lombardi, P., et al. (2018) · Advances in Biological Regulation · doi:10.1016/j.jbior.2018.06.002 · Cited by 36
Park, M., Upton, D., Blackmon, M., Dixon, V., Craver, S., Neal, D., & Perkins, D. (2018) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-018-2139-3 · Cited by 37
“More recently, mutations in Ataxia Telangiectasia Mutated (ATM) have been identified in patients with familial pancreatic cancer [9].”
BackgroundTug of War between Survival and Death: Exploring ATM Function in Cancer
Stagni, V., Oropallo, V., Fianco, G., Antonelli, M., Cinà, I., & Barilà, D. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15045388 · Cited by 32
Screening for Pancreatic Cancer
Ngamruengphong, S., & Canto, M. I. (2016) · Surgical Clinics of North America · doi:10.1016/j.suc.2016.07.016 · Cited by 30
Astiazarán-Symonds, E., & Goldstein, A. M. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-021-01806-y · Cited by 34
Rosenthal, E. T., Evans, B. A., Kidd, J., Brown, K. L., Gorringe, H., van Orman, M., & Manley, S. (2016) · Journal of the American College of Radiology · doi:10.1016/j.jacr.2016.10.003 · Cited by 30
Human Correlates of Provocative Questions in Pancreatic Pathology
McDonald, O. G., Maitra, A., & Hruban, R. H. (2012) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e318273f998 · Cited by 30
Self-citationFeng, Y., Liu, H., Duan, B., Liu, Z., Abbruzzese, J. L., Walsh, K. M., Zhang, X., & Wei, Q. (2019) · Carcinogenesis · doi:10.1093/carcin/bgz029 · Cited by 29
ATM Serine/Threonine Kinase and its Role in Pancreatic Risk
Nanda, N., & Roberts, N. J. (2020) · Genes · doi:10.3390/genes11010108 · Cited by 30
“Next-generation s quencing of familial pancrea ic cancer (FPC) patients provided the first conclusive evidence that ATM was a pancreatic cancer susceptibility gene [19].”
BackgroundSelf-citationPrevalence of deleterious ATM germline mutations in gastric cancer patients
Huang, D., Tao, H., He, X., Long, M., Yu, S., Xia, Y., Wei, Z., Xiong, Z., Jones, S., He, Y., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5944 · Cited by 30
“Germline mutations in ATM have also been associated with a moderately increased risk for breast cancer and pancreatic cancer [15, 18].”
BackgroundGenomic profiling guides the choice of molecular targeted therapy of pancreatic cancer
Frank, T. S., Sun, X., Zhang, Y., Yang, J., Fisher, W. E., Gingras, M., & Li, M. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.04.009 · Cited by 28
“Similar genetic variations in several inherited genetic disorders, like Lynch syndrome caused by the DNA mismatch repair (MMR) mutations, and hereditary breast-ovarian cancer caused by the BRCA mutations, also account for 5–10% of pancreatic cancer, especially familial pancreatic cancer [12; 13; 14].”
BackgroundThe Protective Role of Symmetric Stem Cell Division on the Accumulation of Heritable Damage
McHale, P. T., & Lander, A. D. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003802 · Cited by 27
Hasson, S. P., Menes, T. S., & Sonnenblick, A. (2020) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s233485 · Cited by 28
Dhooge, M., Baert‐Desurmont, S., Corsini, C., Caron, O., Andrieu, N., Berthet, P., Bonadona, V., Cohen‐Haguenauer, O., Pauw, A. D., Delnatte, C., et al. (2020) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2020.104080 · Cited by 28
Smith, A. L., Wong, C., Cuggia, A., Borgida, A., Holter, S., Hall, A., Connor, A. A., Bascuñana, C., Asselah, J., Bouganim, N., et al. (2018) · JCO Precision Oncology · doi:10.1200/po.17.00098 · Cited by 29
Self-citationPharmacotherapeutic strategies for treating pancreatic cancer: advances and challenges
Diab, M., Azmi, A. S., Mohammad, R. M., & Philip, P. A. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1561869 · Cited by 28
“in ATM are observed in 2% to 3% of cases of familial pancreatic cancer [13,50,51].”
BackgroundGenomic alterations in pancreatic cancer and their relevance to therapy
Takai, E., & Yachida, S. (2015) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v7.i10.250 · Cited by 27
Walsh, N., Zhang, H., Hyland, P. L., Yang, Q., Mocci, E., Zhang, M., Childs, E. J., Collins, I. J., Wang, Z., Arslan, A. A., et al. (2018) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djy155 · Cited by 29
Self-citation
Metadata
- Authors
- Roberts, N. J., Jiao, Y., Yu, J., Kopelovich, L., Petersen, G. M., Bondy, M. L., Gallinger, S., Schwartz, A. G., Syngal, S., Cote, M. L., Axilbund, J., Schulick, R., Ali, S. Z., Eshleman, J. R., Velculescu, V. E., Goggins, M., Vogelstein, B., Papadopoulos, N., Hruban, R. H., Kinzler, K. W., & Klein, A. P.
- Affiliations
- Brigham and Women's Hospital (US)
- Authors' Affiliations: 1Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center; Departments of 2Medicine, 3Pathology, 4Surgery, and 5Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions; 6Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland; 7Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland; 8Division of Epidemiology, Mayo Clinic, Rochester, Minnesota; 9Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas; 10Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; 11Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan; 12Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts
- Mayo Clinic (US)
- Corresponding author
- Hruban, Ralph H.
- Kinzler, Kenneth W.
- Klein, Alison P.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2012-01-01
- Volume
- 2
- Issue
- 1
- Pages
- 41-46
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC3676748
- OpenAlex
- W2146542392
- Cited by
- 491
- References
- 30
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 22 · 2023: 27 · 2022: 30 · 2021: 49 · 2020: 36 · 2019: 43 · 2018: 42 · 2017: 38 · 2016: 49 · 2015: 41 · 2014: 38 · 2013: 31 · 2012: 20
- FWCI
- 14.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01pc35145-19-0-7, n01cn43302-6-0-1, 5r01ca121113-15)
- National Cancer Institute (N01 CN043302, R01CA-97075, CA123483, R01CA123483, R01-CA121113, N01 PC035145, CA-121113, N01 PC 35145, CA057345, P50CA102701, R01CA057345, R01CA097075, N01-CN 43302, P50CA062924, R37CA057345, CA 62924)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- ATM gene, hereditary pancreatic cancer, pancreatic ductal adenocarcinoma, hereditary cancer predisposition, loss of heterozygosity, constitutional mutation, cancer susceptibility genes, hereditary cancer
- MeSH terms
- Ataxia Telangiectasia, DNA-Binding Proteins, Humans, Mutation, Pancreatic Neoplasms, Pedigree, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, Tumor Suppressor Proteins, Genome-Wide Association Study, Exome, Ataxia Telangiectasia Mutated Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
