CHK1 frameshift mutations in genetically unstable colorectal and endometrial cancers.
The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian cells. In its coding region it presents a sequence of nine consecutive adenines that are a potential site of mutations in tumors with microsatellite instability (MSI). We analyzed the presence of frameshift mutations in the CHK1 gene in human colon and endometrial cancer samples. In the same cancer samples genes known to be altered in these tumors (BAX, TGFBRII, and IGFIIR) were also analyzed. CHK1 frameshfit mutations were found in 1 out 10 colon cancers and 2 out of 7 endometrial cancers showing MSI. CHK1 alterations were associated with the presence of a high degree of MSI. No alterations were found in patients with tumors showing low frequency or lacking instability (microsatellite stable). The same was true for the other four genes analyzed. The insertion or deletion of one A in the poly A tract resulted in a truncated protein. Alterations of the CHK1 gene could represent an alternative way of cancer cells to escape from cell cycle control. Genes Chromosomes Cancer 26:176-180, 1999.
Bertoni
F
F
Molecular Pharmacology Unit, Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.
Codegoni
A M
AM
Furlan
D
D
Tibiletti
M G
MG
Capella
C
C
Broggini
M
M
D014408:Biomarkers, Tumor / Q000235:genetics; D000071877:Checkpoint Kinase 1; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1