Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years.
Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. In this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G>T transitions and 1 G>A) and one in codon 13 (G>A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2. The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal cancer of later age of onset.
Alsop
Kathryn
K
Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Vic., Australia.
Mead
Leeanne
L
Smith
Letitia D
LD
Royce
Simon G
SG
Tesoriero
Andrea A
AA
Young
Joanne P
JP
Haydon
Andrew
A
Grubb
Garry
G
Giles
Graham G
GG
Jenkins
Mark A
MA
Hopper
John L
JL
Southey
Melissa C
MC
D000328:Adult; D000367:Age Factors; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*