Abstract
PTEN/MMAC1 is a candidate tumor suppressor gene recently identified at chromosomal band 10q23. It is mutated in sporadic brain, breast, and prostate cancer and in the germ line of patients with hereditary Cowden disease. We searched for genetic alterations of the PTEN/MMAC1 gene in 39 primary head and neck cancers (HNSCCs), 42 primary non-small cell lung cancers (NSCLCs), 80 pancreatic cancer xenografts, and 37 cell lines and xenografts from colon, lung, and gastric cancers. Microsatellite analysis revealed loss of heterozygosity at markers near the gene in 41% of primary HNSCCs, 50% of NSCLCs, and 39% of the pancreatic cancers. Three cases of HNSCCs displayed homozygous deletion involving the gene. We sequenced the entire coding region of the PTEN/MMAC1 gene in the remaining tumors displaying loss of heterozygosity and found one terminating mutation in a HNSCC sample. Thus, a second inactivation event was observed in 4 of 39 primary HNSCC cases. By use of a protein truncation assay, one terminating mutation was also identified in one of eight NSCLC cell lines. Our results suggest that PTEN/MMAC1 gene inactivation plays a role in the genesis of some tumor types.
Footnotes
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↵1 Supported by the Specialized Program of Research Excellence (SPORE) in Lung Cancer CA-58184, the SPORE in Gastrointestinal Cancer CA-62924, and the James Valvano Foundation for Cancer Research.
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↵2 To whom requests for reprints should be addressed, at Head and Neck Cancer Research Division, The Johns Hopkins University, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196. Phone: (410) 550-5130; Fax: (410) 614-1411; E-mail: jenjin@welchlink.welch.jhu.edu.
- Received August 13, 1997.
- Accepted November 19, 1997.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 3
