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Search for Mutations and Examination of Allelic Expression Imbalance of the p73 Gene at 1p36.33 in Human Lung Cancers¹

Laboratories of Ultrastructure Research [S. N., N. H., M. K., H. K., Takao T., Takas. T.] and Immunology [To. T.], Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan

We examined 61 lung cancer cases to determine whether alterations of p73, a novel monoallelically expressed p53-like molecule, may be involved in the pathogenesis of lung cancer. Allelic loss at the p73 locus at 1p36.33 was observed in 42% (11 of 26 informative cases), and squamous cell carcinoma tended to carry this lesion most frequently. Somatic mutations in the p73 gene itself, however, were not detected, despite our extensive search. We found interindividual difference in the allelic expression of p73 in normal lung, as well as intertissue variance, even within the same individual, but preferential loss of the expressed allele appeared to be an unlikely mechanism for p73 inactivation. This study, consequently, suggests the presence of an as yet unidentified tumor suppressor gene or genes within the subtelomeric region of 1p, warranting further studies aimed at its isolation.

¹ This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture, Japan, as well as by a Grant-in-Aid for the Second Term Comprehensive Ten-Year Strategy for Cancer Control and by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed, at Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.

Received 12/23/97. Accepted 2/17/98.

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