Novel mutations of neurofibromatosis type 1 gene in small cell lung cancers.

Abstract

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. DNA was extracted from the tumors, and single-strand conformation polymorphism and direct sequencing were used to detect mutations. 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. A mutation in this region could imply a poor prognosis.