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Diagnostic and Therapeutic Nuclear Medicine for Neuroendocrine Tumors pp 127–140Cite as

Molecular Genetics of Gastroenteropancreatic Neuroendocrine Tumours

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Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) can be divided to subgroups depending on their localization. Genetics of pancreatic neuroendocrine tumours (PNETs) is relatively well characterized, with frequent germline or somatic mutations in MEN1, VHL, TSC1/TSC2 and NF1 and somatic mutations in ATRX/DAXX, YY1 as well as members of the mTOR signalling pathway. Mutations in YY1 have so far been reported only in insulin-producing tumours. Most frequent chromosomal aberrations were observed in 6q, 11q, 11p, 20p and 21. The genetics of small intestinal neuroendocrine tumours is, however, more or less unknown. On the other hand, more information about chromosomal aberrations has been reported, pointing out chromosome 18 and 11 as being frequently altered in SI-NETs. While a significant portion of PNETs is part of familial syndromes with known genetic background, almost no information is available for other gastroenteropancreatic neuroendocrine tumours. In this chapter we present the current knowledge of genetics involved in gastroenteropancreatic neuroendocrine tumorigenesis.

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References

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

    Article  CAS  PubMed  Google Scholar 

  2. Vortmeyer AO, et al. Non-islet origin of pancreatic islet cell tumors. J Clin Endocrinol Metab. 2004;89(4):1934–8.

    Article  CAS  PubMed  Google Scholar 

  3. Perren A, et al. 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. J Clin Endocrinol Metab. 2007;92(3):1118–28.

    Article  CAS  PubMed  Google Scholar 

  4. Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25(3):458–511.

    Article  CAS  PubMed  Google Scholar 

  5. Halfdanarson TR, et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol. 2008;19(10):1727–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lubensky IA, et al. Multiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease patients: histopathological and molecular genetic analysis. Am J Pathol. 1998;153(1):223–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Crippa S, et al. Surgical management of insulinomas: short- and long-term outcomes after enucleations and pancreatic resections. Arch Surg. 2012;147(3):261–6.

    Article  PubMed  Google Scholar 

  8. Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16(3):363–71.

    Article  CAS  PubMed  Google Scholar 

  9. Underdahl LO, Woolner LB, Black BM. Multiple endocrine adenomas; report of 8 cases in which the parathyroids, pituitary and pancreatic islets were involved. J Clin Endocrinol Metab. 1953;13(1):20–47.

    Article  CAS  PubMed  Google Scholar 

  10. Thakker RV. Multiple endocrine neoplasia type 1 (MEN1). Best Pract Res Clin Endocrinol Metab. 2010;24(3):355–70.

    Article  CAS  PubMed  Google Scholar 

  11. Thakker RV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011.

    Article  CAS  PubMed  Google Scholar 

  12. Larsson C, et al. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988;332(6159):85–7.

    Article  CAS  PubMed  Google Scholar 

  13. Bystrom C, et al. Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. Proc Natl Acad Sci U S A. 1990;87(5):1968–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chandrasekharappa SC, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276(5311):404–7.

    Article  CAS  PubMed  Google Scholar 

  15. Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 2008;29(1):22–32.

    Article  CAS  PubMed  Google Scholar 

  16. Machens A, et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol (Oxf). 2007;67(4):613–22.

    Google Scholar 

  17. Thompson NW, et al. MEN I pancreas: a histological and immunohistochemical study. World J Surg. 1984;8(4):561–74.

    Article  CAS  PubMed  Google Scholar 

  18. Lonser RR, et al. von Hippel-Lindau disease. Lancet. 2003;361(9374):2059–67.

    Article  CAS  PubMed  Google Scholar 

  19. Libutti SK, et al. Pancreatic neuroendocrine tumors associated with von Hippel Lindau disease: diagnostic and management recommendations. Surgery. 1998;124(6):1153–9.

    Article  CAS  PubMed  Google Scholar 

  20. Binkovitz LA, Johnson CD, Stephens DH. Islet cell tumors in von Hippel-Lindau disease: increased prevalence and relationship to the multiple endocrine neoplasias. AJR Am J Roentgenol. 1990;155(3):501–5.

    Article  CAS  PubMed  Google Scholar 

  21. Blansfield JA, et al. Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs). Surgery. 2007;142(6):814–8; discussion 818 e1–2.

    Article  PubMed  Google Scholar 

  22. Latif F, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993;260(5112):1317–20.

    Article  CAS  PubMed  Google Scholar 

  23. Iwai K, et al. Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proc Natl Acad Sci U S A. 1999;96(22):12436–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Maxwell PH, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399(6733):271–5.

    Article  CAS  PubMed  Google Scholar 

  25. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355(13):1345–56.

    Article  CAS  PubMed  Google Scholar 

  26. van Slegtenhorst M, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277(5327):805–8.

    Article  PubMed  Google Scholar 

  27. European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75(7):1305–15.

    Article  Google Scholar 

  28. Tee AR, et al. Tuberous sclerosis complex-1 and −2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002;99(21):13571–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gutman A, Leffkowitz M. Tuberous sclerosis associated with spontaneous hypoglycaemia. Br Med J. 1959;2(5159):1065–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dworakowska D, Grossman AB. Are neuroendocrine tumours a feature of tuberous sclerosis? A systematic review. Endocr Relat Cancer. 2009;16(1):45–58.

    Article  CAS  PubMed  Google Scholar 

  31. Jiao Y, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011;331(6021):1199–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Williams VC, et al. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123(1):124–33.

    Article  PubMed  Google Scholar 

  33. North K. Neurofibromatosis type 1. Am J Med Genet. 2000;97(2):119–27.

    Article  CAS  PubMed  Google Scholar 

  34. Ozonoff S. Cognitive impairment in neurofibromatosis type 1. Am J Med Genet. 1999;89(1):45–52.

    Article  CAS  PubMed  Google Scholar 

  35. Maertens O, et al. Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet. 2006;15(6):1015–23.

    Article  CAS  PubMed  Google Scholar 

  36. Listernick R, Charrow J, Gutmann DH. Intracranial gliomas in neurofibromatosis type 1. Am J Med Genet. 1999;89(1):38–44.

    Article  CAS  PubMed  Google Scholar 

  37. Bausch B, et al. Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1. J Clin Endocrinol Metab. 2007;92(7):2784–92.

    Article  CAS  PubMed  Google Scholar 

  38. Wallace MR, et al. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990;249(4965):181–6.

    Article  CAS  PubMed  Google Scholar 

  39. Ballester R, et al. The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell. 1990;63(4):851–9.

    Article  CAS  PubMed  Google Scholar 

  40. Xu GF, et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell. 1990;62(3):599–608.

    Article  CAS  PubMed  Google Scholar 

  41. Xu GF, et al. The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell. 1990;63(4):835–41.

    Article  CAS  PubMed  Google Scholar 

  42. Anlauf M, et al. Hereditary neuroendocrine tumors of the gastroenteropancreatic system. Virchows Arch. 2007;451 Suppl 1:S29–38.

    Article  PubMed  Google Scholar 

  43. Perren A, et al. Pancreatic endocrine tumors are a rare manifestation of the neurofibromatosis type 1 phenotype: molecular analysis of a malignant insulinoma in a NF-1 patient. Am J Surg Pathol. 2006;30(8):1047–51.

    Article  PubMed  Google Scholar 

  44. Nishi T, et al. A case of pancreatic neuroendocrine tumor in a patient with neurofibromatosis-1. World J Surg Oncol. 2012;10:153.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Niemeijer ND, et al. Succinate dehydrogenase (SDH)-deficient pancreatic neuroendocrine tumor expands the SDH-related tumor spectrum. J Clin Endocrinol Metab. 2015;100(10):E1386–93.

    Article  CAS  PubMed  Google Scholar 

  46. Gill AJ, et al. Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Hum Pathol. 2010;41(6):805–14.

    Article  CAS  PubMed  Google Scholar 

  47. King A, Selak MA, Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene. 2006;25(34):4675–82.

    Article  CAS  PubMed  Google Scholar 

  48. Jochmanova I, et al. Hypoxia-inducible factor signaling in pheochromocytoma: turning the rudder in the right direction. J Natl Cancer Inst. 2013;105(17):1270–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cao Y, et al. Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1. Nat Commun. 2013;4:2810.

    PubMed  Google Scholar 

  50. Cromer MK, et al. Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas. Proc Natl Acad Sci U S A. 2015;112(13):4062–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lichtenauer UD, et al. Frequency and clinical correlates of somatic Ying Yang 1 mutations in sporadic insulinomas. J Clin Endocrinol Metab. 2015;100(5):E776–82.

    Article  PubMed  CAS  Google Scholar 

  52. Hessman O, et al. Mutation of the multiple endocrine neoplasia type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas. Cancer Res. 1998;58(3):377–9.

    CAS  PubMed  Google Scholar 

  53. Zhuang Z, et al. Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Res. 1997;57(21):4682–6.

    CAS  PubMed  Google Scholar 

  54. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12(1):9–22.

    Article  CAS  PubMed  Google Scholar 

  55. Li J, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–7.

    Article  CAS  PubMed  Google Scholar 

  56. Samuels Y, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.

    Article  CAS  PubMed  Google Scholar 

  57. Sato T, et al. Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer. Oncogene. 2010;29(18):2746–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yao JC, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lewis PW, et al. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc Natl Acad Sci U S A. 2010;107(32):14075–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Marinoni I, et al. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology. 2014;146(2):453–60. e5.

    Article  CAS  PubMed  Google Scholar 

  61. Heaphy CM, et al. Altered telomeres in tumors with ATRX and DAXX mutations. Science. 2011;333(6041):425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fishbein L, et al. Whole-exome sequencing identifies somatic ATRX mutations in pheochromocytomas and paragangliomas. Nat Commun. 2015;6:6140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Schwartzentruber J, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482(7384):226–31.

    Article  CAS  PubMed  Google Scholar 

  64. Pipinikas CP, et al. Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2015;22(3):L13–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Rigaud G, et al. High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications. Cancer Res. 2001;61(1):285–92.

    CAS  PubMed  Google Scholar 

  66. Stricker I, et al. Site- and grade-specific diversity of LINE1 methylation pattern in gastroenteropancreatic neuroendocrine tumours. Anticancer Res. 2012;32(9):3699–706.

    PubMed  Google Scholar 

  67. Choi IS, et al. Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol. 2007;20(7):802–10.

    Article  CAS  PubMed  Google Scholar 

  68. Pizzi S, et al. RASSF1A promoter methylation and 3p21.3 loss of heterozygosity are features of foregut, but not midgut and hindgut, malignant endocrine tumours. J Pathol. 2005;206(4):409–16.

    Article  CAS  PubMed  Google Scholar 

  69. Liu L, et al. Epigenetic alterations in neuroendocrine tumors: methylation of RAS-association domain family 1, isoform A and p16 genes are associated with metastasis. Mod Pathol. 2005;18(12):1632–40.

    CAS  PubMed  Google Scholar 

  70. Dammann R, et al. Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic carcinoma. Oncogene. 2003;22(24):3806–12.

    Article  CAS  PubMed  Google Scholar 

  71. Malpeli G, et al. Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors. BMC Cancer. 2011;11:351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Modali SD, et al. Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic neuroendocrine tumors. Mol Endocrinol. 2015;29(2):224–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Modlin IM, et al. A three-decade analysis of 3,911 small intestinal neuroendocrine tumors: the rapid pace of no progress. Am J Gastroenterol. 2007;102(7):1464–73.

    Article  PubMed  Google Scholar 

  74. Yao JC, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72.

    Article  PubMed  Google Scholar 

  75. Akerstrom G, et al. Management of midgut carcinoids. J Surg Oncol. 2005;89(3):161–9.

    Article  PubMed  Google Scholar 

  76. Boudreaux JP, et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum. Pancreas. 2010;39(6):753–66.

    Article  PubMed  Google Scholar 

  77. Banck MS, et al. The genomic landscape of small intestine neuroendocrine tumors. J Clin Invest. 2013;123(6):2502–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Francis JM, et al. Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet. 2013;45(12):1483–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Georgitsi M, et al. Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab. 2007;92(8):3321–5.

    Article  CAS  PubMed  Google Scholar 

  80. Pellegata NS, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006;103(42):15558–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Crona J, et al. Somatic mutations and genetic heterogeneity at the CDKN1B locus in small intestinal neuroendocrine tumors. Ann Surg Oncol. 2015;22 Suppl 3:1428–35.

    Article  Google Scholar 

  82. Lollgen RM, et al. Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer. 2001;92(6):812–5.

    Article  CAS  PubMed  Google Scholar 

  83. Karpathakis A, et al. Prognostic impact of novel molecular subtypes of small intestinal neuroendocrine tumor. Clin Cancer Res. 2016;22(1):250–8.

    Article  CAS  PubMed  Google Scholar 

  84. Kytola S, et al. Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. Am J Pathol. 2001;158(5):1803–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Verdugo AD, et al. Global DNA methylation patterns through an array-based approach in small intestinal neuroendocrine tumors. Endocr Relat Cancer. 2014;21(1):L5–7.

    Article  CAS  PubMed  Google Scholar 

  86. Neklason DW, et al. Evidence for a heritable contribution to neuroendocrine tumors of the small intestine. Endocr Relat Cancer. 2016;23(2):93–100.

    Article  PubMed  Google Scholar 

  87. Hemminki K, Li X. Familial carcinoid tumors and subsequent cancers: a nation-wide epidemiologic study from Sweden. Int J Cancer. 2001;94(3):444–8.

    Article  CAS  PubMed  Google Scholar 

  88. Sei Y, et al. A hereditary form of small intestinal carcinoid associated with a Germline Mutation in inositol polyphosphate multikinase. Gastroenterology. 2015;149(1):67–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Xu R, et al. Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death. Sci Signal. 2013;6(269):ra22.

    PubMed  PubMed Central  Google Scholar 

  90. Rindi G, et al. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology. 1993;104(4):994–1006.

    Article  CAS  PubMed  Google Scholar 

  91. Bordi C, et al. The antral mucosa as a new site for endocrine tumors in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndromes. J Clin Endocrinol Metab. 2001;86(5):2236–42.

    CAS  PubMed  Google Scholar 

  92. Lehy T, et al. Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome. Gut. 1992;33(9):1275–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Debelenko LV, et al. The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology. 1997;113(3):773–81.

    Article  CAS  PubMed  Google Scholar 

  94. Hoffmann KM, Furukawa M, Jensen RT. Duodenal neuroendocrine tumors: classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol. 2005;19(5):675–97.

    Article  CAS  PubMed  Google Scholar 

  95. Pipeleers-Marichal M, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med. 1990;322(11):723–7.

    Article  CAS  PubMed  Google Scholar 

  96. Karasawa Y, et al. Duodenal somatostatinoma and erythrocytosis in a patient with von Hippel-Lindau disease type 2A. Intern Med. 2001;40(1):38–43.

    Article  CAS  PubMed  Google Scholar 

  97. Maddock IR, et al. A genetic register for von Hippel-Lindau disease. J Med Genet. 1996;33(2):120–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Pacak K, et al. New syndrome of paraganglioma and somatostatinoma associated with polycythemia. J Clin Oncol. 2013;31(13):1690–8.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59.

    Article  PubMed  Google Scholar 

  100. Stinner B, Rothmund M. Neuroendocrine tumours (carcinoids) of the appendix. Best Pract Res Clin Gastroenterol. 2005;19(5):729–38.

    Article  CAS  PubMed  Google Scholar 

  101. Rindi G, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449(4):395–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Rindi G, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451(4):757–62.

    Article  CAS  PubMed  Google Scholar 

  103. Takizawa N, et al. Molecular characteristics of colorectal neuroendocrine carcinoma; similarities with adenocarcinoma rather than neuroendocrine tumor. Hum Pathol. 2015;46(12):1890–900.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Experimental Surgery, Department of Surgical Sciences, Uppsala University, Uppsala University Hospital, Building 70, 75185, Uppsala, Sweden

    Samuel Backman MB & Peyman Björklund MD, PhD

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  1. Samuel Backman MB
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  2. Peyman Björklund MD, PhD
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Correspondence to Peyman Björklund MD, PhD .

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  1. Section on Medical Neuroendocrinology, Eunice Kennedy Shriver NICHD, NIH, Bethesda, Maryland, USA

    Karel Pacak

  2. Department of Nuclear Medicine, Aix-Marseille University, Marseille, France

    David Taïeb

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Backman, S., Björklund, P. (2017). Molecular Genetics of Gastroenteropancreatic Neuroendocrine Tumours. In: Pacak, K., Taïeb, D. (eds) Diagnostic and Therapeutic Nuclear Medicine for Neuroendocrine Tumors. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-46038-3_6

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