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Frequent Microsatellite Instability in Primary Small Cell Lung Cancer¹

Division of Head and Neck Cancer Research, Departments of Otolaryngology [A. M., D. S.], Oncology [D. S., M. M., S. B. B.], and Pathology [E. G.], Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, and Department of Pathology, Duke University, Durham, North Carolina 27706 [R. V.]

Alterations in microsatellite sequences characterize hereditary nonpolyposis colorectal cancer. This microsatellite instability is due in some kindreds to a germline mutation of the mismatch repair gene hMSH2 on chromosome 2p. Although microsatellite alterations have been reported in other hereditary nonpolyposis colorectal cancer-associated tumors including endometrial and gastric cancers, such changes were not detected in most other major neoplasms. We found that 15 of 33 (45%) primary small cell lung cancers, tumors not found in the hereditary nonpolyposis colorectal cancer syndrome, displayed alterations of microsatellite loci which consisted of deletions or expansions of (CA)_n dinucleotide repeats. In 8 of these 15 neoplasms, microsatellite instability was detected in more than 10% of all tested alleles. However, small cell lung cancers that revealed instability contained widespread allelic loss and had a uniformly poor prognosis. These results expand considerably the known spectrum of tumors with microsatellite instability.

¹ Supported by grants of Lung Spore CA-58184-01 and "Schweizerische Stiftung für medizinisch-biologische Stipendien" (to A. M.)

² To whom reprint requests should be adressed: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205.

Received 2/16/94. Accepted 3/14/94.

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