The Study of CDKN2/p16INK4A Mutation in Human Breast Cancer

Song, Tae Jin; Lee, Eun Sook; Kwon, Jeong Ah; Kim, Chong Suk; Bae, Jeoung Won; Koo, Bum Hwan

Abstract

The p16 is a cyclin-dependent kinase inhibitor(CDKI) that inhibits cell cycle progression. In recent studies, homozygous deletions of p16 gene have been noted in some cancer cell lines, which implies the deletion or mutation of p16 gene may contribute to the malignant progression of cells in some ways. This study was to investigate the frequency of p16 gene mutation in breast cancer patients by using polymerase chain reaction-single stranded confromational polymorphysm(PCR-SSCP) analysis. Examination of 24 blood samples and corresponding 16 tissue samples from 24 breast cancer patients were performed by PCR-SSCP method. Four from 24 blood samples(16.7%) disclosed 3 abnormal bands and one band shifting. Among 13 tissue samples revealed three conformational changes(23.1%). In two cases, there were abnormal bands in both blood samples and cancer tissues. One case with no products by PCR in the tissue sample showed a band shifting in the blood sample. Three cases with no PCR products in tissue samples may considered as total allelic deletion of the p16. The cases of abnormal PCR-SSCP results show some abnormalities on direct sequencing by Sanger method as T base insertion, C/T and A/G bases substitution. The results may suggest some of breast cancer patients have germline mutations of the p16 gene and some have somatic mutations. In the carcinogenesis of some breast cancers, p16 gene mutation may dysregulates the cell cycle, that may play an important role in the unlimited tumor cell proliferations.