Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer.
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 mesotheliomas 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 (approximately 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.
Sekido
Y
Y
Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas 75235.
Pass
H I
HI
Bader
S
S
Mew
D J
DJ
Christman
M F
MF
Gazdar
A F
AF
Minna
J D
JD
D001483:Base Sequence; D002892:Chromosomes, Human, Pair 22; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D016515:Genes, Neurofibromatosis 2; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008654:Mesothelioma / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025721:WT1 Proteins