KRAS mutation profile in colorectal carcinoma and novel mutation--internal tandem duplication in KRAS.
Oncogenic KRAS mutations are associated with resistance to anti-EGFR therapy in colorectal carcinoma. Since anti-EGFR monoclonal antibodies are employed in clinical practice in advanced colorectal cancer, KRAS mutations have become an important predictor of therapy outcome. Mutational analysis of KRAS was performed on 163 adenocarcinoma samples. Exons 1-3 of KRAS were analyzed using SSCP and sequencing. Fifty seven (35%) carcinomas had missense point mutations in one of codons 12, 13, 59, 61, 117. In accordance with the published data, missense mutations in codons 12 (66%) and 13 (22%) were the most frequent. Mutations in codons 59 and 117 occurred with the same frequency as in codon 61. The only detected insertion occurred in exon 2. 15-bp insertion resulted in tandem duplication of codons 62-66. Presumably, 5 additional amino acids affected switch II conformation and sustained Ras activity due to decreased GTP hydrolysis. We report this unusual new type mutation.
Wójcik
Piotr
P
Chair and Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Kraków. piotr.wojcik@uj.edu.pl
Kulig
Jan
J
Okoń
Krzysztof
K
Zazula
Monika
M
Moździoch
Ilona
I
Niepsuj
Anna
A
Stachura
Jerzy
J
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D020080:Tandem Repeat Sequences / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins