INFREQUENCY OF BRCA2 ALTERATIONS IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Alterations of BRCA2 result in increased susceptibility to breast canc er in both men and women (relative lifetime risks of 0.06 and 0.8 resp ectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10157 b p. Other cancers that have been described in BRCA2 mutation carriers i nclude those of the larynx. Human chromosome 13q has been shown previo usly by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the r ole of BRCA2 in the development of these cancers. Only 6/22 (27%) of t he laryngeal cancers we examined demonstrated LOH of the BRCA2-contain ing region. These and 10 other HNSCCs of different origins that were d emonstrated by LOH studies to have lost the region of chromosome 13 co ntaining BRCA2 were examined for alterations in this gene. SSCP analys is failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as ye t, unidentified tumor suppressor gene(s). Interestingly tumors with LO H in this region (proximal to D13S118) were far more likely to be deri ved from women than men. This is unusual since HNSCCs are usually four fold more common in men than in women.