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Alterations of CDKN2 (p16) in non‐small cell lung cancer
Author(s) -
Vos Sven De,
Miller Carl W.,
Takeuchi Seisho,
Gombart Adrian F.,
Cho Steve K.,
Koeffler H. Phillip
Publication year - 1995
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870140303
Subject(s) - loss of heterozygosity , exon , biology , point mutation , tumor suppressor gene , microbiology and biotechnology , chromosome , cancer research , single strand conformation polymorphism , lung cancer , gene , mutation , genetics , carcinogenesis , allele , pathology , medicine
The cyclin‐dependent kinase inhibitor known as p16 ( CDK41, CDKN2, INK4A, MTS1 ) has been proposed as a tumor suppressor gene on chromosome segment 9p21. We have evaluated CDKN2 alterations in 34 non‐small cell lung cancers (NSCLCs) with matched normal tissue controls and in 9 NSCLC cell lines by Southern blotting, single‐strand conformation polymorphism (SSCP) with the polymerase chain reaction, and direct sequencing. In addition, loss of heterozygosity at chromosome segment 9p21, with the use of the microsatellite marker D9S171, was studied in these samples. Whereas CDKN2 was either deleted or mutated in NSCLC cell lines at a high frequency (6/9, 67%), alterations were much less frequent (7/34, 21%) in primary tumor samples. Only one sample contained a point mutation in exon 1 of CDKN2. In addition, two samples had homozygous deletions of CDKN2 in exon 1; one had a homozygous and three a hemizygous deletion of exon 2. Possibly normal tissue contaminating our tumor samples may have masked homozygous deletions in these cases. Four patient samples had LOH in the region of CDKN2 on chromosome segment 9p21; two of these samples had potentially inactivating alterations of CDKN2 ; one sample had a mutation of CDKN2 , and the other had a homozygous deletion of exon 1. In summary, inactivation of CDKN2 is implicated in the development of about 20% of NSCLC, but the possibility of another tumor suppressor gene on chromosome segment 9p21 important in lung cancer cannot be eliminated.