Low somatic K- ras mutation frequency in colorectal cancer diagnosed under the age of 45 years

• Published in: European journal of cancer (1990) Vol. 42; no. 10; pp. 1357 - 1361
• Main Authors: Alsop, Kathryn, Mead, Leeanne, Smith, Letitia D., Royce, Simon G., Tesoriero, Andrea A., Young, Joanne P., Haydon, Andrew, Grubb, Garry, Giles, Graham G., Jenkins, Mark A., Hopper, John L., Southey, Melissa C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-07-2006; Elsevier
• Subjects: Adult; Age Factors; Biological and medical sciences; Colorectal Neoplasms - genetics; Early-onset colorectal cancer; Female; Genes, ras - genetics; Humans; Immunohistochemistry; K- ras mutations; Male; Medical sciences; Microsatellite Repeats; Mutation - genetics; Pharmacology. Drug treatments; Tumors; Early-onset colorectal cancer; K- ras mutations; Rectal disease; Colorectal cancer; Pharmacology; Malignant tumor; Low frequency; Colonic disease; K ras Gene; Somatic mutation; Cancerology; Age of onset; C-Onc gene; Digestive diseases; Intestinal disease; Early; Diagnosis; Onc gene; Ras gene; K-ras mutations; Protooncogene
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2006.02.023

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.