Genetic instability occurs in the majority of young patients with colorectal cancer

Bo Liu; Susan M. Farrington; Gloria M. Petersen; Stanley R. Hamilton; Ramon Parsons; Nickolas Papadopoulos; Takato Fujiwara; Jin Jen; Kenneth W. Kinzler; Andrew H. Wyllie; Bert Vogelstein; Malcolm G. Dunlop

doi:10.1038/nm0495-348

Genetic instability occurs in the majority of young patients with colorectal cancer

Bo Liu, Susan M. Farrington, Gloria M. Petersen, Stanley R. Hamilton, Ramon Parsons, Nickolas Papadopoulos, Takato Fujiwara, Jin Jen, Kenneth W. Kinzler, Andrew H. Wyllie, Bert Vogelstein, Malcolm G. Dunlop

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301 Scopus citations

Abstract

Replication errors (RER) associated with genetic instability have been found in cancers of several different types and particularly in the tumours of patients with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined the prevalence of such instability in relation to age among patients without HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or younger exhibited instability (58% of 31 patients), whereas CRCs from patients older than 35 uncommonly did (12% of 158, P <0.0001). Twelve of the patients under 35 with instability were evaluated for alterations of mismatch repair genes, and five were found to harbour germline mutations. These data suggest that the mechanisms underlying tumour development in young CRC patients differ from those in most older patients, regardless of HNPCC status. The results have important implications for genetic testing and management of young CRC patients and their families.

Original language	English (US)
Pages (from-to)	348-352
Number of pages	5
Journal	Nature Medicine
Volume	1
Issue number	4
DOIs	https://doi.org/10.1038/nm0495-348
State	Published - Apr 1 1995

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1038/nm0495-348

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title = "Genetic instability occurs in the majority of young patients with colorectal cancer",

abstract = "Replication errors (RER) associated with genetic instability have been found in cancers of several different types and particularly in the tumours of patients with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined the prevalence of such instability in relation to age among patients without HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or younger exhibited instability (58% of 31 patients), whereas CRCs from patients older than 35 uncommonly did (12% of 158, P <0.0001). Twelve of the patients under 35 with instability were evaluated for alterations of mismatch repair genes, and five were found to harbour germline mutations. These data suggest that the mechanisms underlying tumour development in young CRC patients differ from those in most older patients, regardless of HNPCC status. The results have important implications for genetic testing and management of young CRC patients and their families.",

author = "Bo Liu and Farrington, {Susan M.} and Petersen, {Gloria M.} and Hamilton, {Stanley R.} and Ramon Parsons and Nickolas Papadopoulos and Takato Fujiwara and Jin Jen and Kinzler, {Kenneth W.} and Wyllie, {Andrew H.} and Bert Vogelstein and Dunlop, {Malcolm G.}",

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AU - Liu, Bo

AU - Farrington, Susan M.

AU - Petersen, Gloria M.

AU - Hamilton, Stanley R.

AU - Parsons, Ramon

AU - Papadopoulos, Nickolas

AU - Fujiwara, Takato

AU - Jen, Jin

AU - Kinzler, Kenneth W.

AU - Wyllie, Andrew H.

AU - Vogelstein, Bert

AU - Dunlop, Malcolm G.

PY - 1995/4/1

Y1 - 1995/4/1

N2 - Replication errors (RER) associated with genetic instability have been found in cancers of several different types and particularly in the tumours of patients with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined the prevalence of such instability in relation to age among patients without HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or younger exhibited instability (58% of 31 patients), whereas CRCs from patients older than 35 uncommonly did (12% of 158, P <0.0001). Twelve of the patients under 35 with instability were evaluated for alterations of mismatch repair genes, and five were found to harbour germline mutations. These data suggest that the mechanisms underlying tumour development in young CRC patients differ from those in most older patients, regardless of HNPCC status. The results have important implications for genetic testing and management of young CRC patients and their families.

AB - Replication errors (RER) associated with genetic instability have been found in cancers of several different types and particularly in the tumours of patients with hereditary non-polyposis colorectal cancer (HNPCC). We have here determined the prevalence of such instability in relation to age among patients without HNPCC. Colorectal cancers (CRCs) in the majority of patients 35 years of age or younger exhibited instability (58% of 31 patients), whereas CRCs from patients older than 35 uncommonly did (12% of 158, P <0.0001). Twelve of the patients under 35 with instability were evaluated for alterations of mismatch repair genes, and five were found to harbour germline mutations. These data suggest that the mechanisms underlying tumour development in young CRC patients differ from those in most older patients, regardless of HNPCC status. The results have important implications for genetic testing and management of young CRC patients and their families.

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Genetic instability occurs in the majority of young patients with colorectal cancer

Abstract

ASJC Scopus subject areas

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