High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss

Matthew H. Kulke, Ellen Freed, Derek Y. Chiang, Juliet Philips, David Zahrieh, Jonathan N. Glickman, Ramesh A. Shivdasani

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1,and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.

Original languageEnglish (US)
Pages (from-to)591-603
Number of pages13
JournalGenes Chromosomes and Cancer
Volume47
Issue number7
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Fingerprint

Carcinoid Tumor
Chromosomes
Chromosomes, Human, Pair 18
Neoplasms
Neuropeptides
Tumor Suppressor Genes
Oncogenes
Small Intestine
Single Nucleotide Polymorphism
Carcinogenesis
Proteins
Staining and Labeling
Drug Therapy
Genes

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. / Kulke, Matthew H.; Freed, Ellen; Chiang, Derek Y.; Philips, Juliet; Zahrieh, David; Glickman, Jonathan N.; Shivdasani, Ramesh A.

In: Genes Chromosomes and Cancer, Vol. 47, No. 7, 01.07.2008, p. 591-603.

Research output: Contribution to journalArticle

Kulke, Matthew H. ; Freed, Ellen ; Chiang, Derek Y. ; Philips, Juliet ; Zahrieh, David ; Glickman, Jonathan N. ; Shivdasani, Ramesh A. / High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. In: Genes Chromosomes and Cancer. 2008 ; Vol. 47, No. 7. pp. 591-603.
@article{c7b043e6313c4a7f94c16f346ceff7ce,
title = "High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss",
abstract = "Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1,and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.",
author = "Kulke, {Matthew H.} and Ellen Freed and Chiang, {Derek Y.} and Juliet Philips and David Zahrieh and Glickman, {Jonathan N.} and Shivdasani, {Ramesh A.}",
year = "2008",
month = "7",
day = "1",
doi = "10.1002/gcc.20561",
language = "English (US)",
volume = "47",
pages = "591--603",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "7",

}

TY - JOUR

T1 - High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss

AU - Kulke, Matthew H.

AU - Freed, Ellen

AU - Chiang, Derek Y.

AU - Philips, Juliet

AU - Zahrieh, David

AU - Glickman, Jonathan N.

AU - Shivdasani, Ramesh A.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1,and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.

AB - Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1,and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.

UR - http://www.scopus.com/inward/record.url?scp=44349100999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44349100999&partnerID=8YFLogxK

U2 - 10.1002/gcc.20561

DO - 10.1002/gcc.20561

M3 - Article

VL - 47

SP - 591

EP - 603

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 7

ER -