Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy

de Wilde, Roeland F.; Edil, Barish H.; Hruban, Ralph H.; Maitra, Anirban

doi:10.1038/nrgastro.2012.9

Cited by 122Neuroendocrine Tumor Research AdvancesPancreatic and Hepatic Oncology ResearchNeurofibromatosis and Schwannoma Cases

Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy

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de Wilde, Roeland F., Edil, Barish H., Hruban, Ralph H., Maitra, Anirban·2012·Nature Reviews Gastroenterology & Hepatology

DOI 10.1038/nrgastro.2012.9PMC PMC3544293

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Abstract

Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ∼1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ∼65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance.

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PDAC accounts for more than 90% of pancreas cancers and has a distinct molecular profile and natural history from pancreatic neuroendocrine tumors.
“PDAC accounts for greater than 90% of pancreas cancers and has a distinct molecular profile and natural history from pancreatic neuroendocrine tumors”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [22]

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Bosman, F. T. (2010) · Medical Entomology and Zoology · Cited by 4,814 · see citing works
One Hundred Years After “Carcinoid”: Epidemiology of and Prognostic Factors for Neuroendocrine Tumors in 35,825 Cases in the United States
Yao, J. C., Hassan, M. M., Phan, A. T., Dagohoy, C. G., Leary, C. C., Mares, J. E., Abdalla, E. K., Fleming, J. B., Vauthey, J., Rashid, A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.4377 · Cited by 4,510 · see citing works
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Nagtegaal, I. D., Odze, R. D., Klimstra, D. S., Paradis, V., Rugge, M., Schirmacher, P., Washington, K. M., Carneiro, F., Cree, I. A., & the WHO Classification of Tumours Editorial Board (2019) · Histopathology · doi:10.1111/his.13975 · Cited by 4,221 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Self-citation
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Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448 · see citing works
Everolimus for Advanced Pancreatic Neuroendocrine Tumors
Yao, J. C., Shah, M. H., Ito, T., Lombard‐Bohas, C., Wolin, E. M., Cutsem, E. V., Hobday, T. J., Okusaka, T., Capdevila, J., de Vries, E. G. E., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1009290 · Cited by 2,879 · see citing works
Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · see citing works
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Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors
Raymond, É., Dahan, L., Raoul, J., Bang, Y., Borbath, I., Lombard‐Bohas, C., Valle, J. W., Metrakos, P. P., Smith, D. M., Vinik, A. I., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1003825 · Cited by 2,567 · see citing works
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O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561 · see citing works
Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group
Rinke, A., Müller, H., Schade‐Brittinger, C., Klose, K., Barth, P. J., Wied, M., Mayer, C., Aminossadati, B., Pape, U., Bläker, M., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.8510 · Cited by 2,507 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
Self-citation
Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis
Pàez‐Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Viñals, F., Inoue, M., Bergers, G., Hanahan, D., & Casanovas, O. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.027 · Cited by 2,344 · see citing works
Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice
Lindahl, P., Johansson, B. R., Levéen, P., & Betsholtz, C. (1997) · Science · doi:10.1126/science.277.5323.242 · Cited by 2,226 · see citing works
Positional Cloning of the Gene for Multiple Endocrine Neoplasia-Type 1
Chandrasekharappa, S. C., Guru, S. C., Manickam, P., Olufemi, S.-E., Collins, F. S., Emmert‐Buck, M. R., Debelenko, L. V., Zhuang, Z., Lubensky, I. A., Liotta, L. A., et al. (1997) · Science · doi:10.1126/science.276.5311.404 · Cited by 2,076 · see citing works
DAXX / ATRX , MEN1 , and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors
Jiao, 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 1,717 · see citing works
Self-citation
von Hippel-Lindau disease
Lonser, R. R., Glenn, G. M., Walther, M. M., Chew, E. Y., Libutti, S. K., Linehan, W. M., & Oldfield, E. H. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13643-4 · Cited by 1,615 · see citing works
Treatment With the Radiolabeled Somatostatin Analog [ 177 Lu-DOTA 0 ,Tyr 3 ]Octreotate: Toxicity, Efficacy, and Survival
Kwekkeboom, D. J., de Herder, W. W., Kam, B. L. R., van Eijck, C. H. J., van Essen, M., Kooij, P. P. M., Feelders, R. A., van Aken, M. O., & Krenning, E. P. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.2553 · Cited by 1,454 · see citing works
Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors
Bergers, G., Song, S., Meyer-Morse, N., Bergsland, E. K., & Hanahan, D. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17929 · Cited by 1,361 · see citing works
Primary Peptic Ulcerations of the Jejunum Associated with Islet Cell Tumors of the Pancreas
Zollinger, R. M., & Ellison, E. H. (1955) · Annals of Surgery · doi:10.1097/00000658-195510000-00015 · Cited by 1,329 · see citing works
Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions
Goldberg, A. D., Banaszynski, L. A., Noh, K., Lewis, P. W., Elsässer, S. J., Stadler, S. C., Dewell, S. B., Law, M. J., Guo, X., Li, X., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.003 · Cited by 1,281 · see citing works
Heritable formation of pancreatic β-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes
Hanahan, D. (1985) · Nature · doi:10.1038/315115a0 · Cited by 1,267 · see citing works
Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors
Bergers, G., Song, S., Meyer-Morse, N., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317929 · Cited by 1,192 · see citing works
Safety, Pharmacokinetic, and Antitumor Activity of SU11248, a Novel Oral Multitarget Tyrosine Kinase Inhibitor, in Patients With Cancer
Faivre, S. J., Delbaldo, C., Vera, K., Robert, C., Lozahic, S., Lassau, N., Bello, C. L., DePrimo, S. E., Brega, N. M., Massimini, G., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.2194 · Cited by 1,162 · see citing works
Altered Telomeres in Tumors with ATRX and DAXX Mutations
Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., et al. (2011) · Science · doi:10.1126/science.1207313 · Cited by 1,083 · see citing works
Self-citation
Streptozocin–Doxorubicin, Streptozocin–Fluorouracil, or Chlorozotocin in the Treatment of Advanced Islet-Cell Carcinoma
Moertel, C. G., Lefkopoulo, M., Lipsitz, S. R., Hahn, R. G., & Klaassen, D. J. (1992) · New England Journal of Medicine · doi:10.1056/nejm199202203260804 · Cited by 968 · see citing works
Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival
Halfdanarson, T. R., Rabe, K. G., Rubin, J., & Petersen, G. M. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn351 · Cited by 895 · see citing works
Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
Lewis, P., Elsaesser, S. J., Noh, K., Stadler, S., & Allis, C. (2010) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1008850107 · Cited by 830 · see citing works
The Akt-mTOR tango and its relevance to cancer
Hay, N. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.08.008 · Cited by 816 · see citing works
First‐line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas
Strosberg, J., Fine, R. L., Choi, J., Nasir, A., Coppola, D., Chen, D., Helm, J. F., & Kvols, L. K. (2010) · Cancer · doi:10.1002/cncr.25425 · Cited by 763 · see citing works
Streptozocin Alone Compared with Streptozocin plus Fluorouracil in the Treatment of Advanced Islet-Cell Carcinoma
Moertel, C. G., Hanley, J. A., & Johnson, L. A. (1980) · New England Journal of Medicine · doi:10.1056/nejm198011203032101 · Cited by 659 · see citing works
Efficacy of RAD001 (Everolimus) and Octreotide LAR in Advanced Low- to Intermediate-Grade Neuroendocrine Tumors: Results of a Phase II Study
Yao, J. C., Phan, A. T., Chang, D. Z., Wolff, R. A., Hess, K. R., Gupta, S. K., Jacob, C., Mares, J. E., Landgraf, A., Rashid, A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.7858 · Cited by 649 · see citing works
Daily Oral Everolimus Activity in Patients With Metastatic Pancreatic Neuroendocrine Tumors After Failure of Cytotoxic Chemotherapy: A Phase II Trial
Yao, J. C., Lombard‐Bohas, C., Baudin, É., Kvols, L. K., Rougier, P. R., Ruszniewski, P. B., Hoosen, S., Peter, J. S., Haas, T., Lebwohl, D., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.2669 · Cited by 648 · see citing works
Menin Associates with a Trithorax Family Histone Methyltransferase Complex and with the Hoxc8 Locus
Hughes, C. M., Rozenblatt–Rosen, O., Milne, T. A., Copeland, T. D., Levine, S. S., Lee, J. C., Hayes, D. N., Shanmugam, K. S., Bhattacharjee, A., Biondi, C., et al. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00081-4 · Cited by 645 · see citing works
Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia
Verner, J. V., & Morrison, A. B. (1958) · The American Journal of Medicine · doi:10.1016/0002-9343(58)90075-5 · Cited by 637 · see citing works
Menin Interacts with the AP1 Transcription Factor JunD and Represses JunD-Activated Transcription
Agarwal, S. K., Guru, S. C., Heppner, C., Erdos, M. R., Collins, R. M., Park, S. Y., Saggar, S. K., Chandrasekharappa, S. C., Collins, F. S., Spiegel, A. M., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80967-8 · Cited by 626 · see citing works
Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors
Kulke, M. H., Lenz, H., Meropol, N. J., Posey, J. A., Ryan, D. P., Picus, J., Bergsland, E. K., Stuart, K. E., Tye, L., Huang, X., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.9020 · Cited by 623 · see citing works
Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas
Kouvaraki, M. A., Ajani, J. A., Hoff, P. M., Wolff, R. A., Evans, D. B., Lozano, R. D., & Yao, J. C. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.04.024 · Cited by 605 · see citing works
Mechanisms of Chromosomal Instability
Thompson, S. L., Bakhoum, S. F. W., & Compton, D. A. (2010) · Current Biology · doi:10.1016/j.cub.2010.01.034 · Cited by 600 · see citing works
Both p16 Ink4a and the p19 Arf -p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse
Bardeesy, N. M., Aguirre, A. J., Chu, G. C., Cheng, K., Lopez, L. V., Hezel, A. F., Feng, B., Brennan, C. W., Weissleder, R., Mahmood, U., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601273103 · Cited by 575 · see citing works
Menin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes
Yokoyama, A., & Cleary, M. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.003 · Cited by 550 · see citing works
Small Cell and Large Cell Neuroendocrine Carcinomas of the Pancreas are Genetically Similar and Distinct From Well-differentiated Pancreatic Neuroendocrine Tumors
Yachida, S., Vakiani, E., White, C. M., Zhong, Y., Saunders, T., Morgan, R., de Wilde, R. F., Maitra, A., Hicks, J. L., Marzo, A. M. D., et al. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3182417d36 · Cited by 536 · see citing works
Self-citation
Pancreatic Endocrine Tumors: Expression Profiling Evidences a Role for AKT-mTOR Pathway
Missiaglia, E., Dalai, I., Barbi, S., Beghelli, S., Falconi, M., Peruta, M. D., Piemonti, L., Capurso, G., Florio, A. D., Fave, G. D., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.5988 · Cited by 535 · see citing works
Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes
Heaphy, C. M., Subhawong, A. P., Hong, S.-M., Goggins, M. G., Montgomery, E. A., Gabrielson, E., Netto, G. J., Epstein, J. I., Lotan, T. L., Westra, W. H., et al. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.06.018 · Cited by 516 · see citing works
Self-citation
Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors
Kulke, M. H., Stuart, K. E., Enzinger, P. C., Ryan, D. P., Clark, J. W., Muzikansky, A., Vincitore, M., Michelini, A. L., & Fuchs, C. S. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.6046 · Cited by 508 · see citing works
One hundred years after.
Fynn, R. W. (1959) · PubMed · Cited by 502 · see citing works
Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management, and controversies
Jensen, R. T., Berna, M. J., Bingham, D. B., & Norton, J. A. (2008) · Cancer · doi:10.1002/cncr.23648 · Cited by 487 · see citing works
A Multitargeted, Metronomic, and Maximum-Tolerated Dose “Chemo-Switch” Regimen is Antiangiogenic, Producing Objective Responses and Survival Benefit in a Mouse Model of Cancer
Pietras, K., & Hanahan, D. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.093 · Cited by 479 · see citing works
A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors
Crabtree, J. S., Scacheri, P. C., Ward, J. M., Garrett-Beal, L. J., Emmert‐Buck, M. R., Edgemon, K., Lorang, D., Libutti, S. K., Chandrasekharappa, S. C., Marx, S. J., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.3.1118 · Cited by 471 · see citing works
Temozolomide as Monotherapy Is Effective in Treatment of Advanced Malignant Neuroendocrine Tumors
Ekeblad, S., Sundin, A., Janson, E. T., Welin, S., Granberg, D. O., Kindmark, H., Dunder, K., Kozlovacki, G., Örlefors, H., Sigurd, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2053 · Cited by 470 · see citing works
Pancreatic involvement in von Hippel–Lindau disease
Hammel, P. R., Vilgrain, V., Terris, B., Penfornis, A., Sauvanet, A., Corréas, J.-M., Chauveau, D., Balian, A., Beigelman‐Aubry, C., O’Toole, D., et al. (2000) · Gastroenterology · doi:10.1053/gast.2000.18143 · Cited by 425 · see citing works
Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27 Kip1 and p18 INK4c
Karnik, S. K., Hughes, C. M., Gu, X., Rozenblatt–Rosen, O., McLean, G. W., Xiong, Y., Meyerson, M. M., & Kim, S. K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503484102 · Cited by 402 · see citing works
Gastrinomas in the Duodenums of Patients with Multiple Endocrine Neoplasia Type 1 and the Zollinger-Ellison Syndrome
Pipeleers-Marichal, M. A., Somers, G., Willems, G., Foulis, A. K., IMRIE, C. W., Bishop, A. E., Polak, J. M., Häcki, W. H., Stamm, B., Heitz, P. U., et al. (1990) · New England Journal of Medicine · doi:10.1056/nejm199003153221103 · Cited by 392 · see citing works
O 6-Methylguanine DNA Methyltransferase Deficiency and Response to Temozolomide-Based Therapy in Patients with Neuroendocrine Tumors
Kulke, M. H., Hornick, J. L., Frauenhoffer, C., Hooshmand, S. M., Ryan, D. P., Enzinger, P. C., Meyerhardt, J. A., Clark, J. W., Stuart, K. E., Fuchs, C. S., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1476 · Cited by 380 · see citing works
Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors
Halfdanarson, T. R., Rubin, J., Farnell, M. B., et al. (2008) · Endocrine Related Cancer · doi:10.1677/erc-07-0221 · Cited by 372 · see citing works
Multiple Endocrine Neoplasia Type 1: Clinical and Genetic Topics
Marx, S. J., Spiegel, A. M., Skarulis, M. C., Doppman, J. L., Collins, F. S., & Liotta, L. A. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-129-6-199809150-00011 · Cited by 366 · see citing works
Telomere Shortening Is Nearly Universal in Pancreatic Intraepithelial Neoplasia
van Heek, N. T., Meeker, A. K., Kern, S. E., Yeo, C. J., Lillemoe, K. D., Cameron, J. L., Offerhaus, G. J. A., Hicks, J. L., Wilentz, R. E., Goggins, M. G., et al. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64432-x · Cited by 363 · see citing works
Self-citation
Pancreatic Islet Cell Carcinoma
Broder, L. E., & Carter, S. K. (1973) · Annals of Internal Medicine · doi:10.7326/0003-4819-79-1-108 · Cited by 349 · see citing works
Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms
Klöppel, G. (2011) · Endocrine Related Cancer · doi:10.1530/erc-11-0013 · Cited by 338 · see citing works
PANCREATIC SOMATOSTATINOMA
Larsson, L., Holst, J. J., Kuhl, C. K., et al. (1977) · The Lancet · doi:10.1016/s0140-6736(77)92113-4 · Cited by 318 · see citing works
90Y-Edotreotide for Metastatic Carcinoid Refractory to Octreotide
Bushnell, D. L., O’Dorisio, T. M., O'Dorisio, M. S., Menda, Y., Hicks, R. J., Cutsem, E. V., Baulieu, J.-L., Borson‐Chazot, F., Anthony, L. B., Benson, A. B., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.8585 · Cited by 303 · see citing works
Metastatic and Locally Advanced Pancreatic Endocrine Carcinomas: Analysis of Factors Associated With Disease Progression
Panzuto, F., Boninsegna, L., Fazio, N., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.0688 · Cited by 285 · see citing works
Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis.
Meeker, A. K., Hicks, J. L., Platz, E. A., March, G. E., Bennett, C., Delannoy, M. J., & Marzo, A. M. D. (2002) · PubMed · Cited by 271 · see citing works
Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme
Hakin-Smith, V., Jellinek, D. A., Levy, D. E., Carroll, T., Teo, M., TIMPERLEY, W. R., McKay, M., Reddel, R. R., & Royds, J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12681-5 · Cited by 267 · see citing works
Mutation and Expression Analyses Reveal Differential Subcellular Compartmentalization of PTEN in Endocrine Pancreatic Tumors Compared to Normal Islet Cells
Perren, A. A., Komminoth, P., Saremaslani, P., Matter, C., Muletta-Feurer, S., Lees, J. A., Heitz, P. U., & Eng, C. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64624-x · Cited by 265 · see citing works
HeterozygousMen1Mutant Mice Develop a Range of Endocrine Tumors Mimicking Multiple Endocrine Neoplasia Type 1
Bertolino, P., Tong, W., Galendo, D., Wang, Z., & Zhang, C. X. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0154 · Cited by 255 · see citing works
Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis
Joyce, J. A., Laakkonen, P., Bernasconi, M., Bergers, G., Ruoslahti, E. I., & Hanahan, D. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00271-x · Cited by 254 · see citing works
Epidemiology Data on 108 MEN 1 Patients From the GTE With Isolated Nonfunctioning Tumors of the Pancreas
Triponez, F., Dosseh, D., Goudet, P., Cougard, P., Bauters, C. C., Murat, A., Cadiot, G., Niccoli, P., Chayvialle, J., Calender, A., et al. (2006) · Annals of Surgery · doi:10.1097/01.sla.0000197715.96762.68 · Cited by 250 · see citing works
Of Mice and MEN1: Insulinomas in a Conditional Mouse Knockout
Crabtree, J. S., Scacheri, P. C., Ward, J. M., McNally, S. R., Swain, G. P., Montagna, C., Hager, J. H., Hanahan, D., Edlund, H., Magnuson, M. A., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6075-6085.2003 · Cited by 248 · see citing works
Targeted Modulation of MGMT: Clinical Implications
Liu, L., & Gerson, S. L. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2543 · Cited by 245 · see citing works
Microadenomatosis of the Endocrine Pancreas in Patients With and Without the Multiple Endocrine Neoplasia Type 1 Syndrome
Anlauf, M., Schlenger, R., Perren, A., Bauersfeld, J., Koch, C. A., Dralle, H., Raffel, A., Knoefel, W. T., Weihe, E., Ruszniewski, P., et al. (2006) · American Journal of Surgical Pathology · doi:10.1097/01.pas.0000194044.01104.25 · Cited by 223 · see citing works
Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity
Garbrecht, N., Anlauf, M., Schmitt, A. M., et al. (2008) · Endocrine Related Cancer · doi:10.1677/erc-07-0157 · Cited by 203 · see citing works
Are Patients with Multiple Endocrine Neoplasia Type I Prone to Premature Death?
Dean, P. G., van Heerden, J. A., Farley, D. R., Thompson, G. B., Grant, C. S., Harmsen, W. S., & Ilstrup, D. M. (2000) · World Journal of Surgery · doi:10.1007/s002680010237 · Cited by 194 · see citing works
Neuroendocrine neoplasms of the gut and pancreas: new insights
Rindi, G., & Wiedenmann, B. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.120 · Cited by 192 · see citing works
Absence of a telomere maintenance mechanism as a favorable prognostic factor in patients with osteosarcoma.
Ulaner, G. A., Huang, H.-Y., Otero, J. E., Zhao, Z., Ben‐Porat, L., Satagopan, J. M., Gorlick, R. G., Meyers, P. A., Healey, J. H., Huvos, A. G., et al. (2003) · PubMed · Cited by 183 · see citing works
The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1
Carty, S. E., Helm, A., Amico, J. A., Clarke, M. R., Foley, T. P., Watson, C. G., & Mulvihill, J. J. (1998) · Surgery · doi:10.1067/msy.1998.93107 · Cited by 180 · see citing works
Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells
Thomsen, J. B., Schr�der, H., Kristinsson, J., Madsen, B., Szumlanski, C. L., Weinshilboum, R. M., Andersen, J. B., & Schmiegelow, K. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990915)86:6 · Cited by 170 · see citing works
MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 sporadic neoplasms reveals alterations in the vast majority of cases
Corbo, V., Dalai, I., Scardoni, M., Barbi, S., Beghelli, S., Bersani, S., Albarello, L., Doglioni, C., Schott, C., Capelli, P., et al. (2010) · Endocrine Related Cancer · doi:10.1677/erc-10-0028 · Cited by 167 · see citing works
Genetic Differences in Endocrine Pancreatic Tumor Subtypes Detected by Comparative Genomic Hybridization
Speel, E. M., Richter, J., Moch, H., et al. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65495-8 · Cited by 162 · see citing works
Von recklinghausen's disease associated with duodenal somatostatinoma: Contrast of duodenal versus pancreatic somatostatinomas
Mao, C., Shah, A., Hanson, D. J., & Howard, J. M. (1995) · Journal of Surgical Oncology · doi:10.1002/jso.2930590116 · Cited by 124 · see citing works
Lack of Efficacy of Streptozocin and Doxorubicin in Patients With Advanced Pancreatic Endocrine Tumors
McCollum, A. D., Kulke, M. H., Ryan, D. P., et al. (2004) · American Journal of Clinical Oncology · doi:10.1097/01.coc.0000135343.06038.eb · Cited by 122 · see citing works
Mutation of Tumor Suppressor Gene Men1 Acutely Enhances Proliferation of Pancreatic Islet Cells
Schnepp, R. W., Chen, Y.-X., Wang, H., Cash, T. C., Silva, A., Diehl, J. A., Brown, E. J., & Hua, X. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4518 · Cited by 119 · see citing works
Endocrine pancreatic tumors with glucagon hypersecretion: a retrospective study of 23 cases during 20 years
Kindmark, H., Sundin, A., Granberg, D. O., Dunder, K., Skogseid, B. M., Janson, E. T., Welin, S., Öberg, K., & Eriksson, B. (2007) · Medical Oncology · doi:10.1007/s12032-007-0011-2 · Cited by 117 · see citing works
Multiple Endocrine Neoplasia Type 1 (MEN1): Loss of One MEN1 Allele in Tumors and Monohormonal Endocrine Cell Clusters But Not in Islet Hyperplasia of the Pancreas
Perren, A. A., Anlauf, M., Henopp, T., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1944 · Cited by 111 · see citing works
Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors)
Öberg, K. (2009) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e328320d845 · Cited by 110 · see citing works
Role of disease‐causing genes in sporadic pancreatic endocrine tumors: MEN1 andVHL
Moore, P. S., Missiaglia, E., Antonello, D., et al. (2001) · Genes Chromosomes and Cancer · doi:10.1002/gcc.1180 · Cited by 106 · see citing works
VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors
Schmitt, A. M., Schmid, S., Rudolph, T. J., et al. (2009) · Endocrine Related Cancer · doi:10.1677/erc-08-0297 · Cited by 104 · see citing works
The risk of subsequent primary malignant diseases after cancers of the colon and rectum a nationwide cohort study
Enblad, P., Adami, H., Glimelius, B., Krusemo, U. B., & Påhlman, L. (1990) · Cancer · doi:10.1002/1097-0142(19900501)65:9 · Cited by 100 · see citing works
Review of the clinical, histological, and molecular aspects of pancreatic endocrine neoplasms
Gumbs, A. A., Moore, P. S., Falconi, M., Bassi, C., Beghelli, S., Modlin, I. M., & Scarpa, A. (2002) · Journal of Surgical Oncology · doi:10.1002/jso.10142 · Cited by 98 · see citing works
Survival Benefit With Proapoptotic Molecular and Pathologic Responses From Dual Targeting of Mammalian Target of Rapamycin and Epidermal Growth Factor Receptor in a Preclinical Model of Pancreatic Neuroendocrine Carcinogenesis
Chiu, C. W., Nozawa, H., & Hanahan, D. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.0198 · Cited by 96 · see citing works
Global expression analysis of well-differentiated pancreatic endocrine neoplasms using oligonucleotide microarrays.
Maitra, A., Hansel, D. E., Argani, P., et al. (2003) · PubMed · Cited by 95 · see citing works
Self-citation
Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2
Hermann, G., Konukiewitz, B., Schmitt, A. M., et al. (2011) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-011-1118-6 · Cited by 90 · see citing works
Mutations in the MEN I gene in sporadic neuroendocrine tumours of gastroenteropancreatic system
Wiedenmann, B., Toliat, M.-R., Berger, W., et al. (1997) · The Lancet · doi:10.1016/s0140-6736(05)63453-8 · Cited by 87 · see citing works
Hereditary pancreatic endocrine tumours
Alexakis, N., Connor, S. J., Ghaneh, P., Lombard, M., Smart, H. L., Evans, J. D., Hughes, M., Garvey, C. J., Vora, J. P., Vinjamuri, S., et al. (2004) · Pancreatology · doi:10.1159/000079616 · Cited by 83 · see citing works
Surgical treatment of gastrointestinal neuroendocrine tumors
Fendrich, V., & Bartsch, D. K. (2011) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-011-0741-7 · Cited by 81 · see citing works
HIRA and Daxx Constitute Two Independent Histone H3.3-Containing Predeposition ComplexesPreprint
Elsaesser, S. J., & Allis, C. D. (2010) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2010.75.008 · Cited by 81 · see citing works
Overexpression of Cyclin D1 Occurs Frequently in Human Pancreatic Endocrine Tumors1
Chung, D. C., Brown, S. B., Graeme‐Cook, F., Seto, M., Warshaw, A. L., Jensen, R. T., & Arnold, A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6937 · Cited by 78 · see citing works
Pancreatic Endocrine Microadenomatosis in Patients With von Hippel-Lindau Disease
Périgny, M., Hammel, P. R., Corcos, O., LaRochelle, O., Giraud, S., Richard, S., Sauvanet, A., Belghiti, J., Ruszniewski, P. B., Bédossa, P., et al. (2009) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181967992 · Cited by 70 · see citing works
Overexpression of Cyclin D1 Occurs Frequently in Human Pancreatic Endocrine Tumors
Chung, D. C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.11.4373 · Cited by 68 · see citing works
Upregulated expression of PDGF receptor beta in endocrine pancreatic tumors and metastases compared to normal endocrine pancreas
Fjällskog, M.-L., Hessman, O., Eriksson, B. K., & Janson, E. T. (2006) · Acta Oncologica · doi:10.1080/02841860601048388 · Cited by 66 · see citing works
Liver Metastases Arising from Well-Differentiated Pancreatic Endocrine Neoplasms Demonstrate Increased VEGF-C Expression
Hansel, D. E., Rahman, A., Hermans, J. J., et al. (2003) · Modern Pathology · doi:10.1097/01.mp.0000077416.68489.50 · Cited by 66 · see citing works
Tuberous sclerosis: unusual associations in four cases.
Ilgren, E. B., & Westmoreland, D. (1984) · Journal of Clinical Pathology · doi:10.1136/jcp.37.3.272 · Cited by 63 · see citing works
Gastroenteropancreatic neuroendocrine tumors: new insights in the diagnosis and therapy
Alexandraki, K., & Kaltsas, G. (2011) · Endocrine · doi:10.1007/s12020-011-9562-2 · Cited by 62 · see citing works
Enhancing mTOR-targeted cancer therapy
Wang, X., & Sun, S. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903225008 · Cited by 58 · see citing works
New drugs in neuroendocrine tumors: rising of new therapeutic philosophies?
Eriksson, B. K. (2010) · Current Opinion in Oncology · doi:10.1097/cco.0b013e32833adee2 · Cited by 43 · see citing works
Malignant endocrine tumor of the pancreas associated with von Recklinghausen's disease
Fujisawa, T., Osuga, T., Maeda, M., Sakamoto, N., Maeda, T., Sakaguchi, K., Onishi, Y., Toyoda, M., Maeda, H., Miyamoto, K., et al. (2002) · Journal of Gastroenterology · doi:10.1007/s535-002-8135-x · Cited by 38 · see citing works
Combination chemotherapy for islet cell carcinoma and metastatic carcinoid tumors with 5-fluorouracil and streptozotocin.
Chernicoff, D., Rm, B., Cw, G., et al. (1979) · PubMed · Cited by 35 · see citing works
Novel Anticancer Agents in Clinical Trials for Well-Differentiated Neuroendocrine Tumors
Faivre, S. J., Sablin, M., Dreyer, C., et al. (2010) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2010.09.006 · Cited by 33 · see citing works
Updated overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) of sunitinib (SU) versus placebo (PBO) for patients (Pts) with advanced unresectable pancreatic neuroendocrine tumors (NET).
Raymond, É., Niccoli, P., Raoul, J., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.4008 · Cited by 25 · see citing works
Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Impact of somatostatin analog use on progression-free survival in the RADIANT-3 trial.
Shah, M. H., Lombard‐Bohas, C., Ito, T., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.4010 · Cited by 22 · see citing works
Impact of prior chemotherapy on progression-free survival in patients (pts) with advanced pancreatic neuroendocrine tumors (pNET): Results from the RADIANT-3 trial.
Pommier, R. F., Wolin, E. M., Panneerselvam, A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.4103 · Cited by 11 · see citing works
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Everolimus in Patients with Advanced Pancreatic Neuroendocrine Tumors (pNET) (RADIANT-3): Updated Safety Results
Hörsch, D., Lombard‐Bohas, C., Lincy, J., et al. (2011) · The Endocrine Society eBooks · doi:10.1210/endo-meetings.2011.part3.or6.or25-2 · Cited by 5 · see citing works
Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Updated results of a randomized, double-blind, placebo-controlled, multicenter, phase III trial (RADIANT-3).
Strosberg, J., Lincy, J., Winkler, R. E., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.4009 · Cited by 5 · see citing works

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Pancreatic cancer: Advances and challenges
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Ferri-Borgogno, S., Barui, S., McGee, A. M., Griffiths, T., Singh, P. K., Piett, C. G., Ghosh, B., Bhattacharyya, S., Singhi, A., Pradhan, K., et al. (2020) · Cancers · doi:10.3390/cancers12092695 · Cited by 22 · see citing works
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Authors: de Wilde, R. F., Edil, B. H., Hruban, R. H., & Maitra, A.
Affiliations: Johns Hopkins University (US)
Corresponding author: Maitra, Anirban
ORCID: Edil, Barish H.
Hruban, Ralph H.
Maitra, Anirban
Venue: Nature Reviews Gastroenterology & Hepatology
Publisher: Springer Science and Business Media LLC
Published: 2012-02-07
Volume: 9
Issue: 4
Pages: 199-208
ISSN: 1759-5045 (ISSN-L)
1759-5053
DOI: 10.1038/nrgastro.2012.9
PMC: PMC3544293
OpenAlex: W2033808368
Cited by: 122
References: 112
Citations by year: 2026: 3 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 3 · 2019: 9 · 2018: 15 · 2017: 11 · 2016: 14 · 2015: 10 · 2014: 8 · 2013: 9 · 2012: 4
FWCI: 1.24
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Gastroenterology & Hepatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Caring for Carcinoid Foundation
National Cancer Institute (P30CA006973)
Topics: Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
Keywords: pancreatic neuroendocrine tumors, well-differentiated neuroendocrine tumors, DAXX, ATRX, mTOR signaling, somatic mutations, mutation analysis, personalized treatment, targeted therapy, prognosis, cancer genetics, clinicopathological features
MeSH terms: Genetic Testing, Humans, Pancreatic Neoplasms, Pharmacogenetics, Neuroendocrine Tumors, Precision Medicine

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Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy

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