title: Loss of 11p11 is a frequent and early event in sporadic nonfunctioning pancreatic neuroendocrine neoplasms.
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.
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, 0372 Oslo, Norway.
authors.forename: Sven-Petter
authors.initials: SP
authors.lastname: Haugvik
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gorunova
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Haugom
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway.
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Eibak
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, 0372 Oslo, Norway.
authors.forename: Ivar Prydz
authors.initials: IP
authors.lastname: Gladhaug
authors.affiliation: Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
authors.affiliation: Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, 0372 Oslo, Norway.
authors.forename: Francesca
authors.initials: F
authors.lastname: Micci
mesh_terms: D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D020732:Cytogenetic Analysis; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*