Loss of 11p11 is a frequent and early event in sporadic nonfunctioning pancreatic neuroendocrine neoplasms

Haugvik,Sven-Petter; Gorunova,Ludmila; Haugom,Lisbeth; Eibak,Anne  Mette; Gladhaug,Ivar  Prydz; Heim,Sverre; Micci,Francesca

doi:10.3892/or.2014.3328

Loss of 11p11 is a frequent and early event in sporadic nonfunctioning pancreatic neuroendocrine neoplasms

Authors:
- Sven-Petter Haugvik
- Ludmila Gorunova
- Lisbeth Haugom
- Anne Mette Eibak
- Ivar Prydz Gladhaug
- Sverre Heim
- Francesca Micci
View Affiliations

Affiliations: Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, 0372 Oslo, Norway, Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway, Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway
Published online on: July 11, 2014 https://doi.org/10.3892/or.2014.3328
Pages: 906-912
Copyright: © Haugvik et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The pathogenesis of sporadic pancreatic neuroendocrine neoplasms (PNENs) is poorly understood. To gain insight into the genetic mechanisms underlying this tumor entity, we performed genome-wide screening of 16 surgical specimens from 15 patients with sporadic PNEN, combining G-band karyotyping and high resolution comparative genomic hybridization (HR-CGH). G-banding revealed abnormal karyotypes in 2 of 10 tumor samples analyzed. DNA copy number changes were detected in 13 samples, whereas three tumors showed a balanced genome. Gains were more frequent than losses in the nonfunctioning tumors (n=13). Common gains were scored at 5p12-13, 4q13-24, 5p15, 5q11-31, and 9q21-22. Common losses were scored at 11p11, 11p14-15, 11q23, 11p12-13, and 11q22. The average number of copy aberrations (ANCA index) was 12 for 13 nonfunctioning primary tumors, 4.8 for the nonfunctioning tumors with low Ki-67 (≥5%), 21.2 for the tumors with high Ki-67 (<5%), 2.5 for small tumors (<3.5 cm), and 17.8 for large tumors (≥3.5 cm). There was a statistically significant difference in the ANCA index between the groups defined by Ki-67 and tumor size. Nonfunctioning tumors with low Ki-67, no distant metastasis and small size had few aberrations detected by HR-CGH, but frequent loss of material from chromosomal band 11p11. The present study indicates the existence of distinct cytogenetic patterns in sporadic nonfunctioning PNEN. Loss of chromosomal band 11p11 might indicate a primary pathogenetic event in these tumors.

View Figures

View References

1	Fendrich V and Bartsch DK: Surgical treatment of gastrointestinal neuroendocrine tumors. Langenbecks Arch Surg. 396:299–311. 2011. View Article : Google Scholar : PubMed/NCBI
2	Hauso O, Gustafsson BI, Kidd M, Waldum HL, Drozdov I, Chan AK and Modlin IM: Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer. 113:2655–2664. 2008. View Article : Google Scholar : PubMed/NCBI
3	Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A and Evans DB: One hundred years after ‘carcinoid’: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 26:3063–3072. 2008.
4	Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, Capella C, Caplin M, Couvelard A, Doglioni C, Delle FG, Fischer L, Fusai G, de Herder WW, Jann H, Komminoth P, de Krijger RR, La RS, Luong TV, Pape U, Perren A, Ruszniewski P, Scarpa A, Schmitt A, Solcia E and Wiedenmann B: TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst. 104:764–777. 2012. View Article : Google Scholar : PubMed/NCBI
5	Bosman FT, Carneiro F, Hruban RH and Theise ND: WHO Classification of Tumours of the Digestive System. 3. 4th edition. International Agency for Research on Cancer (IARC); Lyon: 2010
6	Rindi G and Wiedenmann B: Neuroendocrine neoplasms of the gut and pancreas: new insights. Nat Rev Endocrinol. 8:54–64. 2011. View Article : Google Scholar : PubMed/NCBI
7	Heim S and Mitelman F: Cancer Cytogenetics. 3rd edition. Wiley-Blackwell; NJ: 2009
8	Capurso G, Festa S, Valente R, Piciucchi M, Panzuto F, Jensen RT and Delle Fave G: Molecular pathology and genetics of pancreatic endocrine tumours. J Mol Endocrinol. 49:R37–R50. 2012. View Article : Google Scholar : PubMed/NCBI
9	Mitelman F, Johansson B and Mertens F: Mitelman database of chromosome aberrations and gene fusion in cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman. 2014
10	Bugalho MJ, Roque L, Sobrinho LG, Hoog A, Nunes JF, Almeida JM, Leitão CN, Santos JR, Pereira MC and Santos MA: Calcitonin-producing insulinoma: clinical, immunocytochemical and cytogenetical study. Clin Endocrinol (Oxf). 41:257–260. 1994. View Article : Google Scholar : PubMed/NCBI
11	Long PP, Hruban RH, Lo R, Yeo CJ, Morsberger LA and Griffin CA: Chromosome analysis of nine endocrine neoplasms of the pancreas. Cancer Genet Cytogenet. 77:55–59. 1994. View Article : Google Scholar : PubMed/NCBI
12	Scappaticci S, Brandi ML, Capra E, Cortinovis M, Maraschio P and Fraccaro M: Cytogenetics of multiple endocrine neoplasia syndrome. II. Chromosome abnormalities in an insulinoma and a glucagonoma from two subjects with MEN1. Cancer Genet Cytogenet. 63:17–21. 1992.PubMed/NCBI
13	Floridia G, Grilli G, Salvatore M, Pescucci C, Moore PS, Scarpa A and Taruscio D: Chromosomal alterations detected by comparative genomic hybridization in nonfunctioning endocrine pancreatic tumors. Cancer Genet Cytogenet. 156:23–30. 2005. View Article : Google Scholar : PubMed/NCBI
14	Speel EJ, Scheidweiler AF, Zhao J, Matter C, Saremaslani P, Roth J, Heitz PU and Komminoth P: Genetic evidence for early divergence of small functioning and nonfunctioning endocrine pancreatic tumors: gain of 9Q34 is an early event in insulinomas. Cancer Res. 61:5186–5192. 2001.PubMed/NCBI
15	Terris B and Bernheim A: Comparative genomic hybridization (CGH): application to the study of neuroendocrine tumors. Ann Pathol. 19(Suppl 5): S9–S11. 1999.(In French).
16	Zhao J, Moch H, Scheidweiler AF, Baer A, Schaffer AA, Speel EJ, Roth J, Heitz PU and Komminoth P: Genomic imbalances in the progression of endocrine pancreatic tumors. Genes Chromosomes Cancer. 32:364–372. 2001. View Article : Google Scholar : PubMed/NCBI
17	Boninsegna L, Panzuto F, Partelli S, Capelli P, Delle FG, Bettini R, Pederzoli P, Scarpa A and Falconi M: Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. Eur J Cancer. 48:1608–1615. 2012. View Article : Google Scholar : PubMed/NCBI
18	Haugvik SP, Marangos IP, Røsok BI, Pomianowska E, Gladhaug IP, Mathisen O and Edwin B: Long-term outcome of laparoscopic surgery for pancreatic neuroendocrine tumors. World J Surg. 37:582–590. 2013. View Article : Google Scholar : PubMed/NCBI
19	Mandahl N: Methods in solid tumors. Human Cytogenetics: A Practical Approach. Vol II: Malignancy and Acquired Abnormalities. Rooney DE and Czepulkowski BH: IRL Press, Oxford University Press; UK: pp. 155–187. 1992
20	Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F and Pinkel D: Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 258:818–821. 1992. View Article : Google Scholar : PubMed/NCBI
21	Micci F, Teixeira MR, Haugom L, Kristensen G, Abeler VM and Heim S: Genomic aberrations in carcinomas of the uterine corpus. Genes Chromosomes Cancer. 40:229–246. 2004. View Article : Google Scholar : PubMed/NCBI
22	Micci F, Haugom L, Ahlquist T, Andersen HK, Abeler VM, Davidson B, Trope CG, Lothe RA and Heim S: Genomic aberrations in borderline ovarian tumors. J Transl Med. 8:212010. View Article : Google Scholar : PubMed/NCBI
23	Speel EJ, Richter J, Moch H, Egenter C, Saremaslani P, Rutimann K, Zhao J, Barghorn A, Roth J, Heitz PU and Komminoth P: Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. Am J Pathol. 155:1787–1794. 1999. View Article : Google Scholar : PubMed/NCBI
24	Jonkers YM, Claessen SM, Perren A, Schmid S, Komminoth P, Verhofstad AA, Hofland LJ, de Krijger RR, Slootweg PJ, Ramaekers FC and Speel EJ: Chromosomal instability predicts metastatic disease in patients with insulinomas. Endocr Relat Cancer. 12:435–447. 2005. View Article : Google Scholar : PubMed/NCBI