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Alterations of retinoblastoma, p53, p16(CDKN2), and p15 genes in human astrocytomas
Author(s) -
Tsuzuki Toshihide,
Tsunoda Shigeru,
Sakaki Toshisuke,
Konishi Noboru,
Hiasa Yoshio,
Nakamura Mitsutoshi
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19960715)78:2<287::aid-cncr15>3.0.co;2-s
Subject(s) - exon , gene , microbiology and biotechnology , biology , point mutation , retinoblastoma , tumor suppressor gene , genetics , silent mutation , mutation , carcinogenesis , missense mutation
BACKGROUND Alterations of the suppressor genes, such as the retinoblastoma (RB), p53, p16(CDKN2), and p15 genes, have been reported in human gliomas. These genes have been suggested as the cell cycle regulatory genes at the G 1 ‐S checkpoint. METHODS Alterations of the RB, p53, p16(CDKN2), and p15 genes in human astrocytomas were screened by single strand conformation polymorphism analysis of polymerase chain reaction products (PCR‐SSCP analysis) and then confirmed by dideoxy sequencing. In addition, the expression of RB and p16 protein was examined by Western blot analysis. RESULTS Aberrations of the RB gene were found in 3 of 23 surgical astrocytoma specimens (13%). Mutations were found at codon 754 in exon 22 (Val→Gly), codon 519 in exon 17 (Thr→Pro), and one base deletion at codon 903 resulting in stop codon at codon 905 in exon 26. These mutational locations were all near the regions associated with the functional domains of the RB gene. Aberrations of the p53 gene were found in 4 cases (17.4%). These mutations were found at codons 146 (Trp→Gly) and 165 (Gln→His) in exon 5, codon 73 (Val→Glu) in exon 4, and codon 313 (Ser→Asn) in exon 9. In addition, alterations of the p16(CDKN2) gene were found, with 5 cases (21.7%) having homozygous deletions, and 2 cases (8.7%) harboring point mutations. No p15 gene alteration was detected. The expression of p16 protein was undetectable in 10 cases (43.5%) by Western blot analysis, demonstrating an inverse correlation with the expression of RB protein. CONCLUSIONS A few cases had overlapping alterations, and the incidence of one or more RB, p53, or p16(CDKN2) changes appeared to be relatively high in human astrocytomas. These results suggest that cell cycle regulatory gene alterations may play an important role in the development of gliomas. Cancer 1996;78:287‐93.