The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Whole-genome landscape of pancreatic neuroendocrine tumours
Abstract
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“substitution signatures were dominated by C>A transversions in NpCpA or NpCpT contexts (Figures 2 and 3) previously associated with inactivation of the BER gene MUTYH [11].”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [11]
Citations
Cites
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
Self-citationIntratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774
voom: precision weights unlock linear model analysis tools for RNA-seq read counts
Law, C. W., Chen, Y., Shi, W., & Smyth, G. K. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r29 · Cited by 6,155
ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking
Wilkerson, M. D., & Hayes, D. N. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq170 · Cited by 5,645
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621
Self-citationMermel, C. H., Schumacher, S. E., Hill, B., Meyerson, M. M., Beroukhim, R., & Getz, G. A. (2011) · Genome biology · doi:10.1186/gb-2011-12-4-r41 · Cited by 3,520
Discovery and saturation analysis of cancer genes across 21 tumour types
Lawrence, M. S., Stojanov, P., Mermel, C. H., Robinson, J. T., Garraway, L. A., Golub, T. R., Meyerson, M., Gabriel, S. B., Lander, E. S., & Getz, G. (2014) · Nature · doi:10.1038/nature12912 · Cited by 3,096
ClinVar: public archive of interpretations of clinically relevant variants
Landrum, M. J., Lee, J. M., Benson, M., Brown, G., Chao, C., Chitipiralla, S., Gu, B., Hart, J., Hoffman, D., Hoover, J., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1222 · Cited by 2,758
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642
Self-citationMassive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414
Flagged first, then by citations
Cited by
Sorted by citations
Pan-cancer analysis of whole genomes
The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Aaltonen, L. A., Abascal, F., Abeshouse, A., Aburatani, H., Adams, D. J., Agrawal, N., Ahn, K. S., Ahn, S.-M., Aikata, H., et al. (2020) · Nature · doi:10.1038/s41586-020-1969-6 · Cited by 3,064
Self-citationPavel, M. E., Öberg, K., Falconi, M., Krenning, E. P., Sundin, A., Perren, A. A., & Berruti, A. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.03.304 · Cited by 1,191
Self-citationRindi, G., Klimstra, D. S., Abedi‐Ardekani, B., Asa, S. L., Bosman, F. T., Brambilla, E. M., BUSAM, K. J., de Krijger, R. R., Dietel, M., El‐Naggar, A. K., et al. (2018) · Modern Pathology · doi:10.1038/s41379-018-0110-y · Cited by 1,164
Self-citationComprehensive Analysis of Hypermutation in Human Cancer
Campbell, B. B., Light, N. D., Fabrizio, D. A., Zatzman, M., Fuligni, F., de Borja, R., Davidson, S., Edwards, M., Elvin, J. A., Hodel, K. P., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.048 · Cited by 778
“Importantly, a similar approach may lead to novel insights and clinical applications in other DNA repair genes, especially for those with a unique signature (Scarpa et al., 2017).”
Consensus guidelines for the use and interpretation of angiogenesis assays
Nowak-Sliwinska, P. M., Alitalo, K. K., Allen, E., Anisimov, A., Aplin, A. C., Auerbach, R., Augustin, H. G., Bates, D. O., B, J. R. V. B., Bender, R. H. F., et al. (2018) · Angiogenesis · doi:10.1007/s10456-018-9613-x · Cited by 619
Gastroenteropancreatic Neuroendocrine Tumors
Cives, M., & Strosberg, J. (2018) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21493 · Cited by 596
Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers
Pozdeyev, N. V., Gay, L. M., Sokol, E. S., Hartmaier, R. J., Deaver, K. E., Davis, S., French, J. D., Borre, P. V., LaBarbera, D. V., Tan, A. C., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0373 · Cited by 545
Signatures of copy number alterations in human cancer
Steele, C. D., Abbasi, A., Islam, S. M. A., Bowes, A. L., Khandekar, A., Haase, K., Hames-Fathi, S., Ajayi, D., Verfaillie, A., Dhami, P., et al. (2022) · Nature · doi:10.1038/s41586-022-04738-6 · Cited by 487
Howe, J. R., Merchant, N. B., Conrad, C. H., Keutgen, X. M., Hallet, J. I., Drebin, J. A., Minter, R. M., Lairmore, T. C., Tseng, J. F., Zeh, H. J., et al. (2019) · Pancreas · doi:10.1097/mpa.0000000000001454 · Cited by 396
Strosberg, J., Halfdanarson, T. R., Bellizzi, A. M., Chan, J. A., Dillon, J. S., Heaney, A. P., Kunz, P. L., O’Dorisio, T. M., Salem, R., Segelov, E., et al. (2017) · Pancreas · doi:10.1097/mpa.0000000000000850 · Cited by 374
Goul, C., Peruzzo, R., & Zoncu, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00641-8 · Cited by 280
“Recent studies have partially clarified this paradoxical situation of the coexistence of constitutively active mTORC1 and dephosphoryl-ated TFEB in BHD.”
BackgroundHofland, J., Falconi, M., Christ, E., Castano, J. P., Faggiano, A., Lamarca, Á., Perren, A. A., Petrucci, S., Prasad, V., Ruszniewski, P. B., et al. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13318 · Cited by 265
“Recently, large scale international collaborative studies are enabling the characterisation through omics approaches of the main molecular layers of Pan-NET.”
InfluentialSelf-citationKos‐Kudła, B., Castano, J. P., Denecke, T., Grande, E., Kjær, A., Koumarianou, A. A., de Mestier, L., Partelli, S., Perren, A. A., Stättner, S., et al. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13343 · Cited by 262
Self-citationSuccinate dehydrogenase (SDH)‐deficient neoplasia
Gill, A. J. (2017) · Histopathology · doi:10.1111/his.13277 · Cited by 263
Self-citationNeuroendocrine Neoplasms: Dichotomy, Origin and Classifications
Klöppel, G. (2017) · Visceral Medicine · doi:10.1159/000481390 · Cited by 248
An Organoid Biobank of Neuroendocrine Neoplasms Enables Genotype-Phenotype Mapping
Kawasaki, K., Toshimitsu, K., Matano, M., Fujita, M., Fujii, M., Togasaki, K., Ebisudani, T., Shimokawa, M., Takano, A., Takahashi, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.023 · Cited by 238
Chan, C. S., Laddha, S. V., Lewis, P. W., Koletsky, M. S., Robzyk, K., da Silva, E. M., Torres, P. J., Untch, B. R., Li, J., Bose, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06498-2 · Cited by 236
Biology and evolution of poorly differentiated neuroendocrine tumors
Rickman, D. S., Beltran, H., Demichelis, F., & Rubin, M. A. (2017) · Nature Medicine · doi:10.1038/nm.4341 · Cited by 230
Bellizzi, A. M. (2019) · Human Pathology · doi:10.1016/j.humpath.2019.12.002 · Cited by 235
“Frequent ATRX inactivation (10–18%) was identified in recent studies defining the molecular genetic landscape of pancreatic NETs [106,107].”
BackgroundAlcala, N., Leblay, N., Gabriel, A., Mangiante, L., Hervás, D., Giffon, T., Sertier, A.-S., Ferrari, A., Derks, J. L., Ghantous, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11276-9 · Cited by 222
“A ccording to the WHO classi fi cation from 2015 1 and a recent IARC-WHO expert consensus proposal 2 , pulmonary carcinoids are low-grade typical and intermediate-grade atypical well-differentiated lung neuroendocrine tumours (LNETs) that belong to the group of lung neuroendocrine neoplasms (LNENs), which also includes…”
BackgroundInfluentialMultiple Endocrine Neoplasia Type 1: Latest Insights
Brandi, M. L., Agarwal, S. K., Perrier, N. D., Lines, K. E., Valk, G. D., & Thakker, R. V. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa031 · Cited by 232
Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms
Mafficini, A., & Scarpa, A. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00160 · Cited by 221
Self-citationAdvances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms
Hofland, J., Kaltsas, G., & de Herder, W. W. (2019) · Endocrine Reviews · doi:10.1210/endrev/bnz004 · Cited by 211
Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis
Ly, P., & Cleveland, D. W. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.08.005 · Cited by 209
Halfdanarson, T. R., Strosberg, J., Tang, L. A., Bellizzi, A. M., Bergsland, E. K., O’Dorisio, T. M., Halperin, D. M., Fishbein, L. M., Eads, J. R., Hope, T. A., et al. (2020) · Pancreas · doi:10.1097/mpa.0000000000001597 · Cited by 205
Paniccia, A., Polanco, P. M., Boone, B. A., Wald, A. I., McGrath, K., Brand, R. E., Khalid, A., Kubiliun, N. M., Lennon, A. M., Park, W. G., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.09.028 · Cited by 213
Kamilaris, C. D. C., & Stratakis, C. A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00339 · Cited by 198
Xu, J., Shen, L., Zhou, Z., Li, J., Bai, C., Chi, Y., Li, Z., Xu, N., Li, E., Liu, T., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30496-4 · Cited by 197
Assarzadegan, N., & Montgomery, E. A. (2020) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2019-0665-ra · Cited by 198
Therapeutic implications of menin inhibition in acute leukemias
Issa, G. C., Ravandi, F., Dinardo, C. D., Jabbour, E. J., Kantarjian, H. M., & Andreeff, M. (2021) · Leukemia · doi:10.1038/s41375-021-01309-y · Cited by 200
The New World Health Organization Classification for Pancreatic Neuroendocrine Neoplasia
Inzani, F. S., Petrone, G., & Rindi, G. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.04.008 · Cited by 189
Ewing sarcoma and Ewing-like tumors
Sbaraglia, M., Righi, A., Gambarotti, M., & Tos, A. P. D. (2019) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-019-02720-8 · Cited by 183
Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors
Cejas, P., Drier, Y., Dreijerink, K. M. A., Brosens, L. A. A., Deshpande, V., Epstein, C. B., Conemans, E. B., Morsink, F. H. M., Graham, M. K., Valk, G. D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0493-4 · Cited by 187
Hackeng, W. M., Brosens, L. A. A., Kim, J. Y., O’Sullivan, R. J., Sung, Y.-N., Liu, T., Cao, D., Heayn, M., Brosnan‐Cashman, J. A., An, S., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-322595 · Cited by 166
Self-citationDigestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms
de Mestier, L., Cros, J. F., Neuzillet, C., Hentic, O., Egal, A., Müller, N., Bouché, O., Cadiot, G., Ruszniewski, P. B., Couvelard, A., et al. (2017) · Neuroendocrinology · doi:10.1159/000475527 · Cited by 163
Ito, T., Masui, T., Komoto, I., Doi, R., OSAMURA, R. Y., Sakurai, A., Ikeda, M., Takano, K., Igarashi, H., Shimatsu, A., et al. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-021-01827-7 · Cited by 161
Classification of pulmonary neuroendocrine tumors: new insights
Pelosi, G., Sonzogni, A., Harari, S. A., Albini, A., Bresaola, E., Marchiò, C., Massa, F., Righi, L., Gatti, G., Papanikolaou, N. K., et al. (2017) · Translational Lung Cancer Research · doi:10.21037/tlcr.2017.09.04 · Cited by 146
“It has been observed that carcinoids and high-grade NE carcinomas in the lung share most of the altered genes, such as mutations, copy number variations and microRNA, even though at different prevalence (24-27,95,157), and that common mutations or chromosomal changes may unexpectedly cluster tumor regardless of histol…”
BackgroundInfluentialComprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System
Yachida, S., Totoki, Y., Noë, M., Nakatani, Y., Horie, M., Kawasaki, K., Nakamura, H., Saito-Adachi, M., Suzuki, M., Takai, E., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0669 · Cited by 161
“Somatic mutations in pancreatic NETs (Panc-NET) have been well characterized (4, 5).”
Genetic and epigenetic drivers of neuroendocrine tumours (NET)
Domenico, A. D., Wiedmer, T., Marinoni, I., & Perren, A. A. (2017) · Endocrine Related Cancer · doi:10.1530/erc-17-0012 · Cited by 145
Konukiewitz, B., Jesinghaus, M., Steiger, K., Schlitter, A. M., Kasajima, A., Sipos, B., Zamboni, G., Weichert, W., Pfarr, N., & Klöppel, G. (2018) · Human Pathology · doi:10.1016/j.humpath.2018.03.018 · Cited by 135
Telomere Maintenance Mechanisms in Cancer
Gaspar, T. B., Sá, A., Lopes, J. M., Sobrinho-Simões, M. A., Soares, P., & Vinagre, J. (2018) · Genes · doi:10.3390/genes9050241 · Cited by 144
“ALT is also suggested to predict metastatic disease and poor survival in these tumours [306,309,311,312,334].”
Backgroundvan Riet, J., van de Werken, H. J. G., Cuppen, E. P. J. G., Eskens, F. A. L. M., Tesselaar, M. E. T., van Veenendaal, L. M., Klümpen, H., Dercksen, M. W., Valk, G. D., Lolkema, M. P., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24812-3 · Cited by 135
Variant classification in precision oncology
Leichsenring, J., Horak, P., Kreutzfeldt, S., Heining, C., Christopoulos, P., Volckmar, A., Neumann, O., Kirchner, M., Ploeger, C., Budczies, J., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32358 · Cited by 131
Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells
Pelosi, E., Castelli, G., & Testa, U. (2017) · Biomedicines · doi:10.3390/biomedicines5040065 · Cited by 128
“In the G2 subgroup, tumors displaying ATRX or DAXX or inactivating mutations of negative regulators of mTOR are associated with poor prognosis [207].”
BackgroundInfluentialHong, X., Qiao, S., Li, F., Wang, W., Jiang, R., Wu, H., Chen, H. H., Liu, L., Peng, J., Wang, J., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-317233 · Cited by 122
An Algorithmic Immunohistochemical Approach to Define Tumor Type and Assign Site of Origin
Bellizzi, A. M. (2020) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000256 · Cited by 131
Neuroendocrine Neoplasms of the Small Bowel and Pancreas
Clift, A. K., Kidd, M. S., Bodei, L., Toumpanakis, C., Baum, R. P., Öberg, K., Modlin, I. M., & Frilling, A. (2019) · Neuroendocrinology · doi:10.1159/000503721 · Cited by 125
Uccella, S., Rosa, S. L., Volante, M., & Papotti, M. G. (2018) · Endocrine Pathology · doi:10.1007/s12022-018-9522-y · Cited by 115
Domenico, A. D., Pipinikas, C., Maire, R., Bräutigam, K., Simillion, C., Dettmer, M. S., Vassella, E., Thirlwell, C., Perren, A. A., & Marinoni, I. (2020) · Communications Biology · doi:10.1038/s42003-020-01479-y · Cited by 115
Role of biomarker tests for diagnosis of neuroendocrine tumours
Hofland, J., Zandee, W. T., & de Herder, W. W. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0082-5 · Cited by 113
Comprehensive Genomic Profiling of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs)
Puccini, A., Poorman, K. A., Salem, M. E., Soldato, D., Seeber, A., Goldberg, R. M., Shields, A. F., Xiu, J., Battaglin, F., Berger, M. D., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1804 · Cited by 110
Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System
Yachida, S., Totoki, Y., Noë, M., Nakatani, Y., Horie, M., Kawasaki, K., Nakamura, H. K., Saito-Adachi, M., Suzuki, M., Takai, E., et al. (2022) · Utrecht University Repository (Utrecht University) · Cited by 112
Simbolo, M., Barbi, S., Fassan, M., Mafficini, A., Alì, G., Vicentini, C., Sperandio, N., Corbo, V., Rusev, B. C., Mastracci, L., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.05.003 · Cited by 108
“Indeed, the immunohistochemical findings in LNETs of the present series parallel those in pancreatic neuroendocrine neoplasms, in which of 80% of cases lacking menin nuclear immunostaining, only 30% revealed MEN1 mutations by sequencing analysis,(36) and subsequent whole-genome analysis showed gross chromosome 11 alte…”
BackgroundSelf-citationNones, K., Johnson, J., Newell, F., Patch, A. M., Thorne, H., Kazakoff, S. H., de Luca, X. M., Parsons, M. T., Ferguson, K., Reid, L. E., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz132 · Cited by 93
“Some somatic mutational signatures are strongly linked to pathogenic germline variants in risk genes that play functional roles in DNA repair; for instance, homologous recombination (HR; BRCA1, BRCA2), mismatch repair (MLH1, MSH2, MSH6) or base excision repair (MUTYH) [7–9 , 11].”
InfluentialSelf-citationGuilmette, J. M., & Nosé, V. (2018) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000201 · Cited by 107
Rindi, G., Klersy, C., Albarello, L., Baudin, É., Bianchi, A., Büchler, M. W., Caplin, M. E., Couvelard, A., Cros, J. F., de Herder, W. W., et al. (2018) · Neuroendocrinology · doi:10.1159/000494355 · Cited by 105
Self-citationThe context-specific role of germline pathogenicity in tumorigenesis
Srinivasan, P., Bandlamudi, C., Jonsson, P., Kemel, Y. M., Chavan, S. S., Richards, A. L., Penson, A. V., Bielski, C. M., Fong, C. J., Syed, A., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00949-1 · Cited by 109
Genetic immune escape landscape in primary and metastatic cancer
Martínez-Jiménez, F., Priestley, P., Shale, C., Baber, J., Rozemuller, E. H., & Cuppen, E. P. J. G. (2023) · Nature Genetics · doi:10.1038/s41588-023-01367-1 · Cited by 109
Lee, L., Ito, T., & Jensen, R. T. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1476492 · Cited by 105
“Discrepancies between these studies may partly result from the small number of patients, and due to the heterogeneity in patient’s background, especially their genetic profile [8,16,145,184].”
BackgroundShi, X., Li, Y., Yuan, Q., Tang, S., Guo, S., Zhang, Y., He, J., Zhang, X., Han, M., Liu, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29857-6 · Cited by 103
Singhi, A. D., & Klimstra, D. S. (2017) · Histopathology · doi:10.1111/his.13408 · Cited by 98
Roy, S., LaFramboise, W. A., Liu, T., Cao, D., Luvison, A., Miller, C., Lyons, M. A., O’Sullivan, R. J., Zureikat, A. H., Hogg, M. E., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.02.026 · Cited by 101
Pea, A., Yu, J., Marchionni, L., Noë, M., Luchini, C., Pulvirenti, A., de Wilde, R. F., Brosens, L. A. A., Rezaee, N., Javed, A. A., et al. (2018) · Annals of Surgery · doi:10.1097/sla.0000000000003022 · Cited by 101
“Several lines of evidence suggest that most small primary chromosome in metastatic and nonmetastatic PanNETs.”
BackgroundMethodInfluentialSelf-citationGenomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
Mafficini, A., & Scarpa, A. (2018) · Journal of Endocrinology · doi:10.1530/joe-17-0560 · Cited by 98
“2013) and a previously unreported base excision-repair (BER) deficiency signature due to the biallelic inactivation of the MUTYH gene due to pathogenic germline mutations and somatic loss of heterozygosity; this signature has been shown therein to be the same of MUTYH-associated polyposis (MAP) of the colon (Scarpa et…”
ResultSelf-citationDLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms
Yao, J. C., Bergsland, E. K., Aggarwal, R. R., Aparicio, A. M., Beltran, H., Crabtree, J. S., Hann, C. L., Ibrahim, T., Byers, L. A., Sasano, H., et al. (2022) · The Oncologist · doi:10.1093/oncolo/oyac161 · Cited by 98
Characterization of the Neuroendocrine Tumor Immune Microenvironment
da Silva, A., Bowden, M., Zhang, S., Masugi, Y., Thorner, A. R., Herbert, Z. T., Zhou, C. W., Brais, L. K., Chan, J. A., Hodi, F. S., et al. (2018) · Pancreas · doi:10.1097/mpa.0000000000001150 · Cited by 94
Enane, F. O., Saunthararajah, Y., & Korc, M. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0919-9 · Cited by 96
The future: genetics advances in MEN1 therapeutic approaches and management strategies
Agarwal, S. K. (2017) · Endocrine Related Cancer · doi:10.1530/erc-17-0199 · Cited by 93
Management of functional neuroendocrine tumors of the pancreas.
Öberg, K. (2018) · Gland surgery · doi:10.21037/gs.2017.10.08 · Cited by 78
Raj, N. P., Shah, R. H., Stadler, Z. K., Mukherjee, S., Chou, J. F., Untch, B. R., Li, J., Kelly, V., Osoba, M., Saltz, L. B., et al. (2018) · JCO Precision Oncology · doi:10.1200/po.17.00267 · Cited by 93
“Other (kidney, spleen, adrenal, adnexa, peritoneum) 5 (6)”
Pituitary neuroendocrine tumors: a model for neuroendocrine tumor classification
Asa, S. L., Mete, Ö., Cusimano, M. D., McCutcheon, I. E., Perry, A., Yamada, S., Nishioka, H., Casar‐Borota, O., Uccella, S., Rosa, S. L., et al. (2021) · Modern Pathology · doi:10.1038/s41379-021-00820-y · Cited by 90
Combination Strategies to Improve Targeted Radionuclide Therapy
Chan, T. G., O’Neill, E., Habjan, C., & Cornelissen, B. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.248062 · Cited by 91
“In recent years, TRT has rapidly grown in popularity, with agents such as [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-DOTATATE), 131 I-metaiodobenzylguanidine ( 131 I-MIBG), Bexxar ® and Zevalin ® now clinically approved for the treatment of low-grade neuroendocrine tumours (NETs), neuroblastoma and non-Hodgkin’s lymp…”
BackgroundInfluentialThe landscape of molecular alterations in pancreatic and small intestinal neuroendocrine tumours
Scarpa, A. (2019) · Annales d Endocrinologie · doi:10.1016/j.ando.2019.04.010 · Cited by 88
Self-citationUccella, S., Rosa, S. L., Metović, J., Marchiori, D., Scoazec, J., Volante, M., Mete, Ö., & Papotti, M. G. (2021) · Endocrine Pathology · doi:10.1007/s12022-020-09660-z · Cited by 90
Diagnostic and Prognostic Biomarkers of Adrenal Cortical Carcinoma
Mete, Ö., Güçer, H., Kefeli, M., & Asa, S. L. (2017) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000943 · Cited by 87
Pelosi, G., Bianchi, F., Dama, E., Simbolo, M., Mafficini, A., Sonzogni, A., Pilotto, S., Harari, S. A., Papotti, M. G., Volante, M., et al. (2018) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-018-2307-3 · Cited by 83
“The recently suggested category of NET G3 in the gastrointestinal tract [6, 27], which has been now introduced in the 2017 WHO classification of endocrine tumours [28], may well represent secondary NETs arising from pre-existing G1/G2 NETs.”
Self-citationWang, H., Bender, A. S., Wang, P., Karaköse, E., Inabnet, W. B., Libutti, S. K., Arnold, A., Lambertini, L., Stang, M., Chen, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00992-9 · Cited by 83
The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines
Hofving, T., Arvidsson, Y., Almobarak, B., Inge, L., Pfragner, R., Persson, M., Stenman, G., Kristiansson, E., Johanson, V., & Nilsson, O. (2018) · Endocrine Related Cancer · doi:10.1530/erc-17-0445 · Cited by 86
Mutational signatures are markers of drug sensitivity of cancer cells
Levatić, J., Salvadores, M., Fuster‐Tormo, F., & Supek, F. (2022) · Nature Communications · doi:10.1038/s41467-022-30582-3 · Cited by 79
“This exceeds the number of drug associations replicated in PRISM involving driver mutations (37), copy-number changes (55), or DNA methylation (64) in the same test.”
BackgroundBodei, L., Schöder, H. M., Baum, R. P., Herrmann, K., Strosberg, J., Caplin, M. E., Öberg, K., & Modlin, I. M. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30323-5 · Cited by 79
Zhou, Y., Liu, S. M., Liu, C., Yang, J., Lin, Q., Zheng, S., Chen, C., Zhou, Q., & Chen, R. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.61717 · Cited by 79
A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
Dumanski, J. P., Rasi, C., Björklund, P., Davies, H., Ali, A. S., Grönberg, M., Welin, S., Sørbye, H., Grønbæk, H., Cunningham, J. L., et al. (2017) · Endocrine Related Cancer · doi:10.1530/erc-17-0196 · Cited by 77
“This matter deserves follow-up studies for both SI-NETs and PAN-NETs.”
InfluentialScoazec, J., & Couvelard, A. (2017) · Annales de Pathologie · doi:10.1016/j.annpat.2017.10.003 · Cited by 78
Current and emerging therapies for PNETs in patients with or without MEN1
Frost, M., Lines, K. E., & Thakker, R. V. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2018.3 · Cited by 77
Pancreatic Neuroendocrine Tumors: Molecular Mechanisms and Therapeutic Targets
Maharjan, C. K., Ear, P. H., Tran, C. G., Howe, J. R., Chandrasekharan, C., & Quelle, D. E. (2021) · Cancers · doi:10.3390/cancers13205117 · Cited by 73
“One of the major conclusions has been that pNETs, unlike PDACs, have a low mutational burden [23,24].”
BackgroundResultInfluentialHistopathological, immunohistochemical, genetic and molecular markers of neuroendocrine neoplasms
Kyriakopoulos, G., Mavroeidi, V., Chatzellis, E., Kaltsas, G., & Alexandraki, K. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.06.27 · Cited by 78
“Moreover, biallelic inactivation of ATRX or DAXX through loss of heterozygosity (LOH) was strongly associated with an increase in telomere length as quantified by whole-genome sequencing data (95) while their mutations promoted alternative lengthening of telomeres (ALT) and chromosomal instability (96,97).”
BackgroundXue, Y., Reid, M. D., Pehlivanoğlu, B., Obeng, R. C., Jiang, H., Memiş, B., Lui, S. K., Sarmiento, J. M., Kooby, D. A., Maithel, S. K., et al. (2020) · Endocrine Pathology · doi:10.1007/s12022-020-09628-z · Cited by 75
Kawasaki, K., Rekhtman, N., Quintanal-Villalonga, À., & Rudin, C. M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00696-0 · Cited by 71
Shamir, E. R., Devine, W. P., Pekmezci, M., Umetsu, S. E., Krings, G., Federman, S., Cho, S., Saunders, T. A., Jen, K., Bergsland, E. K., et al. (2018) · Modern Pathology · doi:10.1038/s41379-018-0131-6 · Cited by 71
Auernhammer, C. J., Spitzweg, C., Angele, M. K., Boeck, S. H., Grossman, A. B., Nölting, S., Ilhan, H., Knösel, T., Mayerle, J. V., Reincke, M., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30401-1 · Cited by 70
Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1
Dreijerink, K. M. A., Timmers, H. T. M., & Brown, M. A. (2017) · Endocrine Related Cancer · doi:10.1530/erc-17-0281 · Cited by 69
Jäkel, C., Bergmann, F., Toth, R., Assenov, Y., van der Duin, D., Strobel, O., Hank, T., Klöppel, G., Dorrell, C., Grompe, M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01118-x · Cited by 69
Busico, A., Maisonneuve, P., Prinzi, N., Pusceddu, S., Centonze, G., Garzone, G., Pellegrinelli, A., Giacomelli, L., Mangogna, A., Paolino, C., et al. (2019) · Neuroendocrinology · doi:10.1159/000503722 · Cited by 68
Goncalves, I., Burbury, K., Michael, M., Iravani, A., Kumar, A. S. R., Akhurst, T. J., Tiong, I. S., Blombery, P. A., Hofman, M. S., Westerman, D., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04389-2 · Cited by 70
“Mutations in genes associated with DNArepair have been described in pancreatic neuroendocrine tumours [22].”
BackgroundMolecular Events in the Natural History of Pancreatic Cancer
Oldfield, L. E., Connor, A. A., & Gallinger, S. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.04.005 · Cited by 65
Lawrence, B. J., Blenkiron, C., Parker, K., Tsai, P., Fitzgerald, S. J., Shields, P., Robb, T. J., Yeong, M. L., Kramer, N., James, S., et al. (2018) · npj Genomic Medicine · doi:10.1038/s41525-018-0058-3 · Cited by 66
Self-citationPulvirenti, A., Javed, A. A., Landoni, L., Jamieson, N. B., Chou, J. F., Miotto, M., He, J., Gonen, M., Pea, A., Tang, L. H., et al. (2019) · Annals of Surgery · doi:10.1097/sla.0000000000003579 · Cited by 64
“Age, yrs, median (range) 57 (19–85) 59 (27–83) 55 (19–85) Sex, n (%) Female 321 (51) 116 (51) 205 (51) Male 311 (49) 110 (49) 201 (49) Functional, n (%) No 540 (85) 215 (95) 325 (80) Yes 90 (14) 11 (5) 79 (19) Unknown 2 (1) 0 (0) 2 (1) Multifocal, n (%) No 618 (98) 216 (96) 402 (99) Yes 14 (2) 10 (4) 5 (1) Primary pan…”
Self-citationScott, A. T., Weitz, M., Breheny, P. J., Ear, P. H., Darbro, B. W., Brown, B. J., Braun, T. A., Li, G., Umesalma, S., Kaemmer, C. A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2884 · Cited by 62
“Other commonly mutated genes include DAXX or ATRX, genes in the mTOR pathway, genes involved in DNA damage repair such as MUTHY, and genes involved in chromatin modification.(17,18) Although mutations in the mTOR pathway are seen in only 12-15% of PNETs, expression and activity level analyses have revealed alterations…”
BackgroundNeuroendocrine neoplasia of the gastrointestinal tract revisited: towards precision medicine
Rindi, G., & Wiedenmann, B. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0391-3 · Cited by 66
Lawlor, R. T., Veronese, N., Pea, A., Nottegar, A., Smith, L., Pilati, C., Demurtas, J., Fassan, M., Cheng, L., & Luchini, C. (2019) · BMC Cancer · doi:10.1186/s12885-019-5424-8 · Cited by 62
Self-citation
Metadata
- Authors
- Initiative, A. P. C. G., Scarpa, A., Chang, D. K., Nones, K., Corbo, V., Patch, A.-M., Bailey, P., Lawlor, R. T., Johns, A. L., Miller, D. K., Mafficini, A., Rusev, B., Scardoni, M., Antonello, D., Barbi, S., Sikora, K. O., Cingarlini, S., Vicentini, C., McKay, S., Quinn, M. C. J., Bruxner, T. J. C., Christ, A. N., Harliwong, I., Idrisoglu, S., McLean, S., Nourse, C., Nourbakhsh, E., Wilson, P. J., Anderson, M. J., Fink, J. L., Newell, F., Waddell, N., Holmes, O., Kazakoff, S. H., Leonard, C., Wood, S., Xu, Q., Nagaraj, S. H., Amato, E., Dalai, I., Bersani, S., Cataldo, I., Dei Tos, A. P., Capelli, P., Davì, M. V., Landoni, L., Malpaga, A., Miotto, M., Whitehall, V. L. J., Leggett, B. A., Harris, J. L., Harris, J., Jones, M. D., Humphris, J., Chantrill, L. A., Chin, V., Nagrial, A. M., Pajic, M., Scarlett, C. J., Pinho, A., Rooman, I., Toon, C., Wu, J., Pinese, M., Cowley, M., Barbour, A., Mawson, A., Humphrey, E. S., Colvin, E. K., Chou, A., Lovell, J. A., Jamieson, N. B., Duthie, F., Gingras, M.-C., Fisher, W. E., Dagg, R. A., Lau, L. M. S., Lee, M., Pickett, H. A., Reddel, R. R., Samra, J. S., Kench, J. G., Merrett, N. D., Epari, K., Nguyen, N. Q., Zeps, N., Falconi, M., Simbolo, M., Butturini, G., Van Buren, G., Partelli, S., Fassan, M., Khanna, K. K., Gill, A. J., Wheeler, D. A., Gibbs, R. A., Musgrove, E. A., Bassi, C., Tortora, G., Pederzoli, P., Pearson, J. V., Waddell, N., Biankin, A. V., & Grimmond, S. M.
- Affiliations
- University of Verona (IT)
- Garvan Institute of Medical Research (AU)
- The University of Queensland (AU)
- Queensland University of Technology (AU)
- Glasgow Royal Infirmary (GB)
- Baylor College of Medicine (US)
- Children's Hospital at Westmead (AU)
- The University of Sydney (AU)
- Fremantle Hospital (AU)
- Royal Adelaide Hospital (AU)
- The University of Melbourne (AU)
- Corresponding author
- Scarpa, Aldo
- Biankin, Andrew V.
- Grimmond, Sean M.
- ORCID
- Scarpa, Aldo
- Chang, David K.
- Corbo, Vincenzo
- Patch, Ann-Marie
- Bailey, Peter
- Lawlor, Rita T.
- Johns, Amber L.
- Mafficini, Andrea
- Rusev, Borislav
- Antonello, Davide
- Barbi, Stefano
- Cingarlini, Sara
- Vicentini, Caterina
- Quinn, Michael C. J.
- Bruxner, Timothy J. C.
- Christ, Angelika N.
- Harliwong, Ivon
- Nourbakhsh, Ehsan
- Wilson, Peter J.
- Anderson, Matthew J.
- Fink, J. Lynn
- Newell, Felicity
- Holmes, Oliver
- Kazakoff, Stephen H.
- Leonard, Conrad
- Wood, Scott
- Nagaraj, Shivashankar Hiriyur
- Bersani, Samantha
- Cataldo, Ivana
- Davì, Maria Vittoria
- Landoni, Luca
- Malpaga, Anna
- Miotto, Marco
- Whitehall, Vicki L. J.
- Leggett, Barbara A.
- Harris, Jonathan
- Jones, Marc D.
- Chantrill, Lorraine A.
- Chin, Venessa
- Nagrial, Adnan M.
- Pajic, Marina
- Scarlett, Christopher J.
- Pinho, Andreia
- Rooman, Ilse
- Toon, Christopher
- Wu, Jianmin
- Pinese, Mark
- Cowley, Mark
- Barbour, Andrew
- Mawson, Amanda
- Colvin, Emily K.
- Chou, Angela
- Jamieson, Nigel B.
- Gingras, Marie-Claude
- Dagg, Rebecca A.
- Lau, Loretta M. S.
- Lee, Michael
- Pickett, Hilda A.
- Reddel, Roger R.
- Samra, Jaswinder S.
- Kench, James G.
- Merrett, Neil D.
- Nguyen, Nam Q.
- Zeps, Nikolajs
- Falconi, Massimo
- Simbolo, Michele
- Partelli, Stefano
- Fassan, Matteo
- Khanna, Kum Kum
- Gill, Anthony J.
- Wheeler, David A.
- Gibbs, Richard A.
- Bassi, Claudio
- Tortora, Giampaolo
- Pearson, John V.
- Waddell, Nicola
- Biankin, Andrew V.
- Grimmond, Sean M.
- Venue
- Nature
- Published
- 2017-02-15
- Volume
- 543
- Issue
- 7643
- Pages
- 65-71
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2589112207
- Cited by
- 999
- References
- 62
- Citations by year
- 2026: 65 · 2025: 101 · 2024: 103 · 2023: 110 · 2022: 126 · 2021: 108 · 2020: 131 · 2019: 89 · 2018: 103 · 2017: 52
- FWCI
- 81.15
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-09-27)
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Pancreatic Cancer UK (RIF2015_A06_Jamieson, FLF2015_04_GLASGOW)
- Wellcome Trust (103721/Z/14/Z)
- Cancer Research UK (23526, 17263, 22533)
- Academy of Medical Sciences (AMS-SGCL9-Jamieson)
- Medical Research Council (MR/N005813/1)
- Topics
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- pancreatic neuroendocrine tumors, mutational signatures, MUTYH, germline mutations, CHEK2, BRCA2, MEN1, VHL, chromatin remodeling, DNA repair, mTOR signaling, telomere maintenance, hypoxia, carcinogenesis
- MeSH terms
- Base Sequence, Calmodulin-Binding Proteins, Chromosome Aberrations, DNA Mutational Analysis, DNA Repair, Female, Humans, Male, Pancreatic Neoplasms, Genome, Human, RNA-Binding Proteins, Telomere, Germ-Line Mutation, Carcinoma, Neuroendocrine, Genomics, RNA-Binding Protein EWS, Chromatin Assembly and Disassembly, DNA Glycosylases, DNA Copy Number Variations, TOR Serine-Threonine Kinases
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
