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Neurofibromatosis Type 2 (NF2) Gene Is Somatically Mutated in Mesothelioma but not in Lung Cancer¹

Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235 [Y. S., S. B., A. F. G., J. D. M.]; Thoracic Oncology Section, Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892 [H. I. P., D. J. Y. M.]; and Department of Radiation Oncology, University of California, San Francisco, California 94143 [M. F. C.]

We have found 16 of 28 small cell lung cancers, 17 of 31 non-small cell lung cancers, 2 of 3 carcinoids, and 12 of 14 mesothellomas that had chromosome 22 cytogenetic abnormalities. To determine whether the neurofibromatosis type 2 (NF2) gene located on chromosome 22 participates in the oncogenesis of these malignancies, we studied DNAs from lung cancer cell lines and mesotheliomas using Southern blot analysis and the single-strand conformation polymorphism (SSCP) technique for mutations covering 8 of the 16 known NF2 exons. We detected 7 mutations in 17 mesotheliomas (41%) within the coding region of NF2 but none in 75 lung cancer cell lines (38 small cell lung cancers, 34 non-small cell lung cancers, and 3 carcinoids). These mutations were found to be somatic when normal tissue was available for testing. Four mesothelioma cell lines had relatively large deletions (10–50 kilobases) in the NF2 gene detectable by Southern blot analysis. Two mesothelioma cell lines had nonsense mutations at codons 57 and 341, respectively. Another mesothelioma obtained as a specimen directly from a patient, had a 10-base pair microdeletion from nucleotide 1004 to nucleotide 1013 causing a frameshift mutation. These results suggest that the NF2 gene participates in the oncogenesis in a subset of mesotheliomas but not in lung cancers.

¹ This work was supported by the Julie Gould Foundation (S. B.), the G. Harold and Leila Y. Mathers Charitable Foundation, and NCI Grant P20 CA58220-01.

² To whom requests for reprints should be addressed, at Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-8590.

Received 12/ 9/94. Accepted 2/ 1/95.

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