Novel mutations of neurofibromatosis type 1 gene in small cell lung cancers.
OBJECTIVE
Mutations in the GTPase-activating protein-related domain (GRD) of the von Recklinghausen neurofibromatosis type 1 (NF1) gene have been reported in several tumors that were not previously associated with NF1. We analyzed 37 cases of lung cancer, including 9 cases of small cell carcinoma, to detect mutations in this domain.


METHODS
DNA was extracted from the tumors, and single-strand conformation polymorphism and direct sequencing were used to detect mutations.


RESULTS
Three cases of small cell carcinoma had mutations in NF1-GRD. There were two incidences of an A --> G transition at the second base of codon 1415 resulting in Glu --> Gly substitution, and one incidence of an A --> G transition at the third base of codon 1411 (Pro) without amino acid substitution. All three patients had both hilar and mediastinal lymphatic metastasis.


CONCLUSIONS
A mutation in this region could imply a poor prognosis.
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Kenichi
K
Furukawa
Noboru
N
Yanai
Michiya
M
Fujita
Yukio
Y
Harada
D000236:Adenoma / Q000235:genetics; D000368:Aged; D018287:Carcinoma, Large Cell / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction