Homozygous Deletions and Loss of Expression of the CDKN2 gene occur frequently in head and neck squamous cell carcinoma cell lines but infrequently in primary tumors

✍ Scribed by William M. Lydiatt; V. V. V. S. Murty; Bruce J. Davidson; Li Xu; Katerina Dyomina; Peter G. Sacks; Stimson P. Schantz; R. S. K. Chaganti

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 405 KB
• Volume: 13
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870130204

✦ Synopsis

Deletion of 9~21-22 is a common genetic alteration in dysplastic. in situ, and invasive head and neck squamous cell carcinoma (HNSCC). However, a candidate tumor suppressor gene (TSG) at this site has thus far not been identified in HNSCC. We report homozygous deletion of the recently identified multiple tumor suppressor I (MTSI)/cyclin-dependent kinase-4-inhibitor (CDKNZ) gene mapped to 9p2 I, which encodes the p I 6 protein, a regulator of cyclin-dependent kinase 4, in six of I 6 HNSCC cell lines. We also show absence of the CDKNZ mRNA in all cell lines with CDKNZ deletion as well as in an additional two cell lines without deletion. Overall, we have identified 9p abnormalities in I2 of I 6 (75%) cell lines, at least nine of which involved CDKNZ. We further demonstrate that the CDKNZ deletion in HNSCC is located within a previously described region of allelic loss between D9S I7 I and IFNW, which spans a 4 cM region of 9p. However, examination of 36 primary tumors revealed genetic alterations in only seven of 36 ( 19%) tumors. These results suggest that genetic alterations at CDKNZ are frequent in HNSCC cell lines, but the role of this gene in primary tumors is less compelling. CDKNZ does not appear to be the only TSG on 9p21 in HNSCC, and our results suggest that another region of deletion exists proximal to the IFNW locus. Genes Chromosom Cancer 13:94-98 (1995).