Molecular evidence for independent origin of multifocal neuroendocrine tumors of the enteropancreatic axis

Terrence M. Katona, Timothy D. Jones, Mingsheng Wang, Fadi W. Abdul-Karim, Oscar Cummings, Liang Cheng

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92%) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis.

Original languageEnglish
Pages (from-to)4936-4942
Number of pages7
JournalCancer Research
Volume66
Issue number9
DOIs
StatePublished - May 1 2006

Fingerprint

Neuroendocrine Tumors
Loss of Heterozygosity
X Chromosome Inactivation
Neoplasms
Clone Cells
Laser Capture Microdissection
Multiple Endocrine Neoplasia Type 1
Carcinoid Tumor
Tumor Suppressor Genes
Chromosomes
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular evidence for independent origin of multifocal neuroendocrine tumors of the enteropancreatic axis. / Katona, Terrence M.; Jones, Timothy D.; Wang, Mingsheng; Abdul-Karim, Fadi W.; Cummings, Oscar; Cheng, Liang.

In: Cancer Research, Vol. 66, No. 9, 01.05.2006, p. 4936-4942.

Research output: Contribution to journalArticle

@article{e9f50d6f64ab46ccb51e84abdcd63964,
title = "Molecular evidence for independent origin of multifocal neuroendocrine tumors of the enteropancreatic axis",
abstract = "Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92{\%}) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94{\%}) cases of multifocal carcinoid tumors and 7 of 8 (88{\%}) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46{\%}) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38{\%}) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8{\%}) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis.",
author = "Katona, {Terrence M.} and Jones, {Timothy D.} and Mingsheng Wang and Abdul-Karim, {Fadi W.} and Oscar Cummings and Liang Cheng",
year = "2006",
month = "5",
day = "1",
doi = "10.1158/0008-5472.CAN-05-4184",
language = "English",
volume = "66",
pages = "4936--4942",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Molecular evidence for independent origin of multifocal neuroendocrine tumors of the enteropancreatic axis

AU - Katona, Terrence M.

AU - Jones, Timothy D.

AU - Wang, Mingsheng

AU - Abdul-Karim, Fadi W.

AU - Cummings, Oscar

AU - Cheng, Liang

PY - 2006/5/1

Y1 - 2006/5/1

N2 - Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92%) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis.

AB - Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92%) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis.

UR - http://www.scopus.com/inward/record.url?scp=33646405442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646405442&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-05-4184

DO - 10.1158/0008-5472.CAN-05-4184

M3 - Article

C2 - 16651451

AN - SCOPUS:33646405442

VL - 66

SP - 4936

EP - 4942

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 9

ER -