NDLI: DNA Sequence Profiles of the Colorectal Cancer Critical Gene Set KRAS-BRAF-PIK3CA-PTEN-TP53 Related to Age at Disease Onset

Content Provider	PubMed Central
Author	Berg, Marianne Danielsen, Stine A. Ahlquist, Terje Merok, Marianne A. Ågesen, Trude H. Vatn, Morten H. Mala, Tom Sjo, Ole H. Arne, Bakka Moberg, Ingvild Fetveit, Torunn Mathisen, Øystein Husby, Anders Sandvik, Oddvar Nesbakken, Arild Espen, Thiis-evensen Lothe, Ragnhild A.
Editor	Chan, Kelvin Yuen Kwong
Abstract	The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients.
Related Links	http://dx.doi.org/10.1371/journal.pone.0013978
Starting Page	13978
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	5
Language	English
Publisher	Public Library of Science
Publisher Date	2010-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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