Document Detail


Genome-wide somatic copy number alterations in low-grade PanINs and IPMNs from individuals with a family history of pancreatic cancer.
MedLine Citation:
PMID:  22723370     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Characterizing the earliest chromosomal alterations of pancreatic precursor neoplasms from individuals with a familial aggregation of pancreatic cancer may provide clues as to the loci of pancreatic cancer susceptibility genes.
EXPERIMENTAL DESIGN: We used Illumina 370/660K SNP arrays to conduct genome-wide copy number analysis in 60 benign neoplasms [58 mostly low-grade pancreatic intraepithelial neoplasias (PanIN) and intraductal papillary mucinous neoplasms (IPMN) and two pancreatic neuroendocrine tumors (PNET)] and matched normal tissues from 16 individuals with a family history of pancreatic cancer. PanINs and IPMNs were analyzed for KRAS codon 12/13 mutations.
RESULTS: Of 40 benign neoplasms with adequate SNP calls and allele ratios, somatic chromosomal copy number changes were identifiable in only nine lesions, including eight of the 38 PanIN/IPMNs (two of which had identical alterations) and one of the two PNETs. Only two precursor lesions had more than one somatic copy number alteration. In contrast, the overwhelming majority (∼95%) of PanINs harbored KRAS mutations. The chromosomal alterations identified included nine chromosomal arms affected by chromosomal loss and two by chromosomal gain. Copy number loss spanning 9p21.3 was identified in three precursor lesions; two precursors had chromosomal losses affecting 6q and 17p.
CONCLUSIONS: Low- and intermediate-grade PanINs and IPMNs from patients with a family history of pancreatic cancer harbor few if any somatic chromosomal alterations. The absence of a locus of recurrent chromosomal loss in most low-grade pancreatic cancer precursor lesions supports the hypothesis that there is no one tumor suppressor gene locus consistently involved in initiating familial pancreatic neoplasia.
Authors:
Seung-Mo Hong; Audrey Vincent; Mitsuro Kanda; Julie Leclerc; Noriyuki Omura; Michael Borges; Alison P Klein; Marcia Irene Canto; Ralph H Hruban; Michael Goggins
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-21
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  18     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-16     Completed Date:  2013-01-10     Revised Date:  2013-08-19    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4303-12     Citation Subset:  IM    
Affiliation:
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Carcinoma, Pancreatic Ductal / genetics*,  pathology*
DNA Copy Number Variations*
Family
Female
Genes, ras
Genome-Wide Association Study
Humans
Loss of Heterozygosity
Male
Middle Aged
Mutation
Neoplasm Grading
Pancreatic Neoplasms / genetics*,  pathology*
Grant Support
ID/Acronym/Agency:
P30 CA006973/CA/NCI NIH HHS; P50 CA062924/CA/NCI NIH HHS; P50-CA62924/CA/NCI NIH HHS; R01 CA097075/CA/NCI NIH HHS; R01 CA120432/CA/NCI NIH HHS; R01-CA120432/CA/NCI NIH HHS; R01-CA97075/CA/NCI NIH HHS
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