Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis
Open accessAbstract
Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed. In PanIN lesions from pancreata of patients with PDAC, there was a stepwise increase in K-ras mutations that correlated with the grade of dysplasia of the PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b, and 2-3 lesions, respectively (trend statistic P <.001). Mutation-enriched polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions associated with chronic pancreatitis (CP) or normal pancreas was low (around 10%). In CP, K-ras mutations were only found after a disease duration of 3 years. The correlation of the incidence of K-ras mutations with the grade of dysplasia in PanIN and the occurrence of these mutations in CP with a duration of more than 3 years underlines the importance of this genetic change for the development of PDAC.
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KRAS mutations were found in 10% of CP lesions and 44% of PDAC lesions, with increase in frequency with progression of PanIN grade.
“KRAS mutations were found in 10% of CP lesions and 44% of PDAC lesions, with an increase in frequency with the progression of PanIN grade [102].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [102]
The Results report K-ras mutations in 10% of PanIN lesions associated with chronic pancreatitis (CP) and 44% of those associated with pancreatic ductal adenocarcinoma (PDAC). Mutation frequency increased with PanIN grade in the PDAC group, but the Results explicitly say it was independent of grade in the CP group. The claim omits that limitation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredKRAS mutations are often early events in tumourigenesis in lung and pancreatic cancers.
“KRAS mutations are often early events in tumourigenesis in lung and pancreatic cancers [41, 42].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [42]
KRAS mutation is detectable in 25% of PanIN-1A and 38% of PanIN-1B lesions.
“KRAS mutation is readily detectable in 25% and 38% of PanIN-1A and PanIN-1B, respectively (55).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [55]
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Presence of Somatic Mutations in Most Early-Stage Pancreatic Intraepithelial Neoplasia
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Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies
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“The most frequent among them are KRAS alterations (85%), which mainly consist of substitution of G12, resulting in a constitutively active protein [141].”
BackgroundKRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma
Morris, J. P., Wang, S. C., & Hebrok, M. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2899 · Cited by 567 · see citing works
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“K-RAS mutations have been identified in the pancreas of healthy individuals (Terhune et al., 1998; Lüttges et al., 1999; Löhr et al., 2005).”
BackgroundInfluentialAddressing the challenges of pancreatic cancer: Future directions for improving outcomes
Hidalgo, M. M., Cascinu, S., Kleeff, J. H., Labianca, R., Löhr, M. J., Neoptolemos, J. P., Real, F. X., Laethem, J. V., & Heinemann, V. (2014) · Pancreatology · doi:10.1016/j.pan.2014.10.001 · Cited by 507 · see citing works
“KRAS is an early mutation occurring in PanIN-1A lesions, suggesting that this alteration may play an important role in the initiation of many PDACs [6,24].”
Self-citationA model for RAS mutation patterns in cancers: finding the sweet spot
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Epidemiology and risk factors for pancreatic cancer
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Self-citationKRAS mutation in pancreatic cancer
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Therapeutic Advances in Pancreatic Cancer
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Inflammation-Induced Tumorigenesis and Metastasis
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Molecular genetics of pancreatic intraepithelial neoplasia
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“a greater rate of KRAS mutation in our study; and this is also supported by other studies using cfDNA (5–20%)(16,29) as well as in analyses of pancreatic tissue.(8,9) In previous studies, KRAS”
ResultUpdate on pancreatic intraepithelial neoplasia.
Hruban, R. H., Maitra, A., & Goggins, M. (2008) · PubMed Central · Cited by 245 · see citing works
Precursor Lesions for Sporadic Pancreatic Cancer: PanIN, IPMN, and MCN
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Ras Activity Levels Control the Development of Pancreatic Diseases
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Chronic pancreatitis, pseudotumors and other tumor-like lesions
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“52 It is interesting that K-ras mutations, which are very common in ductal adenocarcinoma, may also occur in the hyperplastic duct epithelium of the pancreas in patients with chronic pancreatitis, particularly with a duration of more than 3 years”
BackgroundSelf-citationPancreatic cancer: advances in treatment.
Mohammed, S., Buren, G. V., & Fisher, W. E. (2014) · PubMed Central · doi:10.3748/wjg.v20.i28.9354 · Cited by 175 · see citing works
Pancreatic Cancer, Inflammation, and Microbiome
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Pathology and Molecular Genetics of Pancreatic Neoplasms
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Drugging KRAS: Current perspectives and state-of-art review
Parikh, K., Banna, G., Liu, S. V., Friedlaender, A., Desai, A., Subbiah, V., & Addeo, A. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01375-4 · Cited by 164 · see citing works
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“While low-grade PanINs (LG-PanINs) are common and low risk, high-grade PanINs (HG-PanINs) are regarded as lesions immediately preceding invasive PDAC and thus are a primary target for intervention [4,5].”
BackgroundResultInfluentialCarpenter, E. S., Elhossiny, A. M., Kadiyala, P., Li, J., McGue, J. J., Griffith, B. D., Zhang, Y., Edwards, J., Nelson, S., Lima, F., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0013 · Cited by 152 · see citing works
Complex role for the immune system in initiation and progression of pancreatic cancer
Inman, K. S. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i32.11160 · Cited by 137 · see citing works
Demographics, Epidemiology, and Inheritance of Pancreatic Ductal Adenocarcinoma
Yeo, T. P. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.12.002 · Cited by 136 · see citing works
Aichler, M., Seiler, C., Tost, M., Siveke, J. T., Mazur, P. K., da Silva‐Buttkus, P., Bartsch, D. K., Langer, P., Chiblak, S., Dürr, A., et al. (2011) · The Journal of Pathology · doi:10.1002/path.3017 · Cited by 131 · see citing works
“In particular, activating mutations of the protooncogene Kras, which are detected in 36%, 44%, and 87% of cancer associated PanIN1A, PanIN1B, and PanIN2-3, respectively, represent the earliest genetic change [7].”
BackgroundSelf-citationFerreira, R. M. M., Sancho, R., Messal, H. A., Nye, E. L., Spencer‐Dene, B., Stone, R. K., Stamp, G., Rosewell, I. R., Quaglia, A., & Behrens, A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.093 · Cited by 130 · see citing works
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Genome profiling of pancreatic adenocarcinoma
Birnbaum, D. J., Adélaïde, J., Mamessier, E., Finetti, P., Lagarde, A., Monges, G., Viret, F., Gonçalvès, A., Turrini, O., Delpero, J., et al. (2011) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20870 · Cited by 122 · see citing works
Mills, L. D., Zhang, Y., Marler, R. J., Herreros‐Villanueva, M., Zhang, L., Almada, L. L., Couch, F. J., Wetmore, C., di Magliano, M. P., & Fernández-Zapico, M. E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.438846 · Cited by 119 · see citing works
The complex landscape of pancreatic cancer metabolism
Sousa, C. M., & Kimmelman, A. C. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu097 · Cited by 123 · see citing works
Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer
Desir, S., O’Hare, P., Vogel, R. I., Sperduto, W., Sarkari, A., Dickson, E. L., Wong, P., Nelson, A., Fong, Y., Steer, C. J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-27649-x · Cited by 120 · see citing works
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“Mutations in the K-ras gene are considered 1 of the earliest genetic events in pancreatic tumorigenesis.(15,29,30) Furthermore, a stepwise increase in K-ras mutations, with an increasing grade of dysplasia in pancreatic intraepithelial neoplasia from patients with ductal adenocarcinoma has been found.”
BackgroundSchönleben, F., Qiu, W., Bruckman, K. C., Ciau, N. T., Li, X., Lauerman, M. H., Frucht, H., Chabot, J. A., Allendorf, J., Remotti, H. E., et al. (2006) · Cancer Letters · doi:10.1016/j.canlet.2006.09.007 · Cited by 113 · see citing works
“The wide variety of the reported frequencies most likely is due to the ongoing better definition of these lesions [7,38,39] and might also be dependent on the sensitivity of a chosen screening methodology [40,41].”
BackgroundPancreatic Intraepithelial Neoplasia Revisited and Updated
Sipos, B., Frank, S., Gress, T. M., Hahn, S. A., & Klöppel, G. (2008) · Pancreatology · doi:10.1159/000178874 · Cited by 112 · see citing works
“Patient age and duration of chronic pancreatitis did not correlate with the grade of PanIN lesions and their K-ras status. Duration was, however, significantly associated with K-ras positivity, as a meta-analysis of published data showed that no case of chronic pancreatitis with a disease duration of less than 3 years…”
ResultSelf-citationSignificance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer
Stefanoudakis, D., Frountzas, M., Schizas, D., Michalopoulos, N. V., Drakaki, A., & Toutouzas, K. G. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46040177 · Cited by 110 · see citing works
CAAX-box protein, prenylation process and carcinogenesis.
Gao, J., Liao, J., & Yang, G. (2009) · PubMed Central · Cited by 103 · see citing works
Fritz, S., Castillo, C. F. F.-D., Mino-Kenudson, M. A., Crippa, S., Deshpande, V., Lauwers, G. Y., Warshaw, A. L., Thayer, S. P., & Iafrate, A. J. (2009) · Annals of Surgery · doi:10.1097/sla.0b013e31819a6e16 · Cited by 103 · see citing works
“Indeed, KRAS mutations seem to be the first known genetic alterations and are detected in approximately 30% of early neoplastic lesions (ie, PanIN-1) with the frequency rising nearly to 100% in PDAC.50 Unlike PDAC where KRAS mutations occur in 90–100%,21,51 many IPMNs did not harbor an active KRAS mutation (60% in our…”
BackgroundInfluentialPancreatic cancer: Current research and future directions
Falasca, M., Kim, M., & Casari, I. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.01.001 · Cited by 100 · see citing works
Brychta, N., Krahn, T., & von Ahsen, O. (2016) · Clinical Chemistry · doi:10.1373/clinchem.2016.257469 · Cited by 101 · see citing works
Inflammation and pancreatic cancer: An updated review
Shadhu, K., & Xi, C. (2018) · Saudi Journal of Gastroenterology · doi:10.4103/sjg.sjg_390_18 · Cited by 94 · see citing works
PAM4-Reactive MUC1 Is a Biomarker for Early Pancreatic Adenocarcinoma
Gold, D. V., Karanjawala, Z., Modrak, D. E., Goldenberg, D. M., & Hruban, R. H. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1488 · Cited by 93 · see citing works
Fischer, C. G., & Wood, L. D. (2018) · The Journal of Pathology · doi:10.1002/path.5154 · Cited by 92 · see citing works
Genetics of familial and sporadic pancreatic cancer
Wood, L. D., Yurgelun, M. B., & Goggins, M. G. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.039 · Cited by 91 · see citing works
Pancreatic Ductal Adenocarcinoma and Its Precursor Lesions
Ren, B., Liu, X., & Suriawinata, A. A. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.10.004 · Cited by 91 · see citing works
“Histologic criteria of invasive adenocarcinoma are haphazard arrangement of neoplastic glands, perineural invasion, vascular invasion, gland immediately adjacent to a muscular artery, luminal necrosis, incomplete lumina, nuclear variation (>4:1) in a single gland, isolated gland in peripancreatic adipose tissue, and a…”
BackgroundTargeted Therapies for Pancreatic Cancer and Hurdles Ahead
Aslan, M., Shahbazi, R., Ulubayram, K., & Özpolat, B. (2018) · Anticancer Research · doi:10.21873/anticanres.13026 · Cited by 88 · see citing works
Kras and tumor immunity: friend or foe?
Cullis, J., Das, S., & Bar-Sagi, D. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031849 · Cited by 85 · see citing works
“The significance of mutant Kras’ cooperation with additional inflammatory diseases in tumorigenesis is emphasized by the observation that oncogenic mutations in Kras have been de- tected in disease-free pancreas of healthy individuals (Terhune et al. 1998; Lüttges et al. 1999; Löhr et al. 2005).”
BackgroundLi, C., Xiao, Z., TONG, J. H. M., To, K., Fang, X., Cheng, A. S. L., & Chen, Y. (2016) · International Journal of Cancer · doi:10.1002/ijc.30414 · Cited by 86 · see citing works
Immervoll, H., Hoem, D., Kugarajh, K., Steine, S. J., & Molven, A. (2006) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-006-0191-8 · Cited by 85 · see citing works
“KRAS mutations are likely to be an early event in pancreatic carcinogenesis as they are often seen in pancreatic intraepithelial neoplasia, increasing in frequency with cellular and architectural atypia [24, 27].”
BackgroundSugimori, M., Sugimori, K., Tsuchiya, H., Suzuki, Y., Tsuyuki, S., Kaneta, Y., Hirotani, A., Sanga, K., Tozuka, Y., Komiyama, S., et al. (2019) · Cancer Science · doi:10.1111/cas.14245 · Cited by 81 · see citing works
“Among them, from 21 subjects (female, N = 7; male, N = 14; age, 64 [27-78] years), serum samples were collected every 4-8 weeks following chemotherapy.”
BackgroundTomita, Y., Azuma, K., Nonaka, Y., Kamada, Y., Tomoeda, M., Kishida, M., Tanemura, M., & Miyoshi, E. (2014) · Pancreas · doi:10.1097/mpa.0000000000000159 · Cited by 82 · see citing works
“The most common genetic alteration in PDAC is the activating mutation of KRAS, which is an initial key event in pancreatic oncogenesis and is found in most cases of PDAC.(34) However, KRAS mutation itself is not sufficient for the development of PDAC; additional genetic alterations and signals from the tumor microenvi…”
BackgroundPrecursor lesions in pancreatic cancer: morphological and molecular pathology
Scarlett, C. J., Salisbury, E., Biankin, A. V., & Kench, J. G. (2011) · Pathology · doi:10.1097/pat.0b013e3283445e3a · Cited by 82 · see citing works
Colby, J. K., Klein, R. D., McArthur, M. J., Conti, C. J., Kiguchi, K., Kawamoto, T., Riggs, P. K., Pavone, A., Sawicki, J. A., & Fischer, S. M. (2008) · Neoplasia · doi:10.1593/neo.08330 · Cited by 81 · see citing works
“Most PDAC cases in humans show mutations in K-ras [64]; however, mutation-specific sequencing failed to show any evidence of signature K-ras mutations in BK5.”
BackgroundHristov, A. C., Cope, L., Cello, F. D., Reyes, M. D., Singh, M., Hillion, J., Belton, A., Joseph, B., Schuldenfrei, A., Iacobuzio–Donahue, C. A., et al. (2009) · Modern Pathology · doi:10.1038/modpathol.2009.139 · Cited by 81 · see citing works
Targeting reactive oxygen species in development and progression of pancreatic cancer
Durand, N., & Störz, P. (2016) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2017.1261017 · Cited by 78 · see citing works
Kamisawa, T., Tsuruta, K., Okamoto, A., Horiguchi, S.-I., Hayashi, Y. K., Yun, X., Yamaguchi, T., & Sasaki, T. (2009) · Pancreas · doi:10.1097/mpa.0b013e3181b65a1c · Cited by 80 · see citing works
“In cancer-associated PanIN lesions, there was a stepwise increase in K-ras mutation that correlated with the grade of dysplasia.(37) However, abnormal changes in the pancreatic duct epithelium were less frequent in patients with AIP than in patients with chronic pancreatitis.”
BackgroundPast Medical History and Pancreatic Cancer Risk: Results From a Multicenter Case-Control Study
Maisonneuve, P., Lowenfels, A. B., Bueno-de-Mesquita, H. B., Ghadirian, P., Baghurst, P., Zatoński, W. A., Miller, A. B., Duell, E. J., Boffetta, P., & Boyle, P. (2010) · Annals of Epidemiology · doi:10.1016/j.annepidem.2009.11.010 · Cited by 79 · see citing works
“Patients with chronic pancreatitis often have similar premalignant changes such as pancreatic intraepithelial neoplasia lesions as are seen in patients with pancreatic cancers (24).”
BackgroundSelf-citationDemographics and Epidemiology of Pancreatic Cancer
Yeo, T. P., & Lowenfels, A. B. (2012) · The Cancer Journal · doi:10.1097/ppo.0b013e3182756803 · Cited by 78 · see citing works
“5 years, there was an association with a high level of K-ras mutation positivity.(67)”
BackgroundSelf-citationGenetic Progression of Pancreatic Cancer
Cowan, R. W., & Maitra, A. (2014) · The Cancer Journal · doi:10.1097/ppo.0000000000000011 · Cited by 76 · see citing works
“Principal among these mutations are activating point mutations in the KRAS oncogene, which are present in as many as 90% of all PDACs(4,5) and are considered an early event in the progression from normal ductal cells to invasive adenocarcinoma.(6,7) The inactivation of several tumor suppressor genes, such as those cod…”
BackgroundKipp, B. R., Fritcher, E. G. B., Clayton, A. C., Gores, G. J., Roberts, L. R., Zhang, J., Levy, M. J., & Halling, K. C. (2010) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2010.100016 · Cited by 77 · see citing works
Haas, S., Jesnowski, R., Steiner, M., Hummel, F., Ringel, J., Burstein, C., Nizze, H., Liebe, S., & Löhr, M. J. (2006) · Europe PMC (PubMed Central) · doi:10.3748/wjg.v12.i30.4843 · Cited by 75 · see citing works
Self-citationBiliary intraepithelial neoplasia in patients without chronic biliary disease
Wu, T., Levy, M. L., Correa, A. M., Rosen, C. B. B., & Abraham, S. C. (2009) · Cancer · doi:10.1002/cncr.24471 · Cited by 74 · see citing works
“Oncogenic K-ras mutations, present in >90% of pancreatic ductal adenocarcinomas, are also found in 10% to 44% of PanIN-1 lesions, depending on whether there is coexistent carcinoma.(23) Loss of p16 expression—corresponding to inactivation of the CDKN2A/INK4A tumor suppressor gene—is seen in 29% of PanIN-1 from pancrea…”
BackgroundPancreatic adenocarcinoma pathology: changing "landscape".
Brosens, L. A. A., Hackeng, W. M., Offerhaus, G. J. A., Hruban, R. H., & Wood, L. D. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2078-6891.2015.032 · Cited by 72 · see citing works
Mori, A., Moser, C., Lang, S. A., Hackl, C., Gottfried, E., Kreutz, M. P., Schlitt, H. J., Geissler, E. K., & Stoeltzing, O. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0525 · Cited by 71 · see citing works
“Because pancreatic cancers frequently harbor activating KRAS mutations (11), which consecutively activate MEK/MAPK/Erk signaling (12), we hypothesized that”
BackgroundPanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration
Bell, A. T. F., Mitchell, J. T., Kiemen, A. L., Lyman, M. R., Fujikura, K., Lee, J. W., Coyne, E. M., Shin, S. M., Nagaraj, S., Deshpande, A. M., et al. (2024) · Cell Systems · doi:10.1016/j.cels.2024.07.001 · Cited by 70 · see citing works
Computational Model Predicts the Effects of Targeting Cellular Metabolism in Pancreatic Cancer
Roy, M., & Finley, S. D. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00217 · Cited by 69 · see citing works
“Mutations mediated by the KRAS or MYC oncogenes, found in 95% of cases of PDAC (Almoguera et al., 1988; Uemura et al., 2004; Löhr et al., 2005; Hezel et al., 2006; Kimmelman, 2015), promote reprogramming of the cellular metabolism, enabling the cancer cells to optimally use available resources…”
BackgroundHarrison, M., Jameson, C., & Gore, M. E. (2007) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2007.01022.x · Cited by 68 · see citing works
Classification, morphology and molecular pathology of premalignant lesions of the pancreas
Cooper, C. L., O'Toole, S. A., & Kench, J. G. (2013) · Pathology · doi:10.1097/pat.0b013e32835f2205 · Cited by 67 · see citing works
“Mutations Mutation of KRAS in 33% of PanIN-1, 44% of PanIN-2 and 87% PanIN-3.(190) Inactivating mutation of CDKN2 in PanIN-2 and telomere shortening in PanIN-1.”
BackgroundAberrant signaling pathways in pancreatic cancer: A two compartment view
McCleary‐Wheeler, A. L., McWilliams, R. R., & Fernández-Zapico, M. E. (2011) · Molecular Carcinogenesis · doi:10.1002/mc.20827 · Cited by 65 · see citing works
“KRAS mutations can be seen in the earliest of lesions in which there is minimal atypia, and these mutations only increase in frequency as the lesions progress through the PanIN lesions to invasive carcinomas [31,32].”
BackgroundCarcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions
Gnoni, A., Licchetta, A., Scarpa, A., Azzariti, A., Brunetti, A. E., Simone, G., Nardulli, P., Santini, D., Aieta, M., Delcuratolo, S., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141019731 · Cited by 64 · see citing works
“Oncogenic KRAS mutations are observed in early pancreatic lesions as previously described [63].”
BackgroundWatts, J. A., Zhang, C., Klein–Szanto, A. J., Kormish, J. D., Fu, J., Zhang, M. Q., & Zaret, K. S. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002277 · Cited by 61 · see citing works
Oncogenic transcription factors: cornerstones of inflammation-linked pancreatic carcinogenesis
Baumgart, S., Ellenrieder, V., & Fernández-Zapico, M. E. (2011) · Gut · doi:10.1136/gutjnl-2011-301008 · Cited by 64 · see citing works
“The most common genetic abnormality in pancreatic cancer is the activating mutation of KRAS, which is an initial key event in pancreatic carcinogenesis and found in virtually all invasively growing tumours.(1) However, mutation of KRAS alone is not sufficient for full neoplastic progression, and additional abnormaliti…”
BackgroundHennig, R., Kehl, T., Noor, S., Ding, X., Rao, S. M., Bergmann, F., Fürstenberger, G., Büchler, M. W., Frieß, H., Krieg, P., et al. (2007) · Neoplasia · doi:10.1593/neo.07565 · Cited by 62 · see citing works
Satellite RNAs promote pancreatic oncogenic processes via the dysfunction of YBX1
Kishikawa, T., Otsuka, M., Yoshikawa, T., Ohno, M., Ijichi, H., & Koike, K. (2016) · Nature Communications · doi:10.1038/ncomms13006 · Cited by 45 · see citing works
Nanofluidic Digital PCR for KRAS Mutation Detection and Quantification in Gastrointestinal Cancer
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The Role of Mitochondria in the Chemoresistance of Pancreatic Cancer Cells
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Ras Activity in Acinar Cells Links Chronic Pancreatitis and Pancreatic Cancer
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Current State of “Omics” Biomarkers in Pancreatic Cancer
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“Previous studies pointed out the most prominent genetic features of PDAC, such as oncogenic activation of K-RAS, which is a standard feature in more than 90% of the patients, and with the early onset mutation of that gene, it is considered a critical driver of PDAC initiation and progression [27].”
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Germline Variants and Risk for Pancreatic Cancer
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- Authors
- Löhr, M., Klöppel, G., Maisonneuve, P., Lowenfels, A. B., & Lüttges, J.
- Affiliations
- Heidelberg University (DE)
- European Institute of Oncology (IT)
- New York Medical College (US)
- Corresponding author
- Löhr, Matthias
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 7
- Issue
- 1
- Pages
- 17-23
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC1490318
- OpenAlex
- W2108100098
- Cited by
- 343
- References
- 66
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 15 · 2023: 15 · 2022: 16 · 2021: 16 · 2020: 17 · 2019: 13 · 2018: 24 · 2017: 22 · 2016: 15 · 2015: 18 · 2014: 26 · 2013: 21 · 2012: 16
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- KRAS mutation, pancreatic ductal adenocarcinoma, pancreatic intraepithelial neoplasia, chronic pancreatitis, pancreatic dysplasia, disease duration
- MeSH terms
- Adenocarcinoma, Humans, Mutation, Pancreatic Ducts, Pancreatic Neoplasms, Pancreatitis, Genes, ras, Carcinoma, Pancreatic Ductal
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