Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer

Inactivation of p53, which represents the most prevalent genetic alteration in lung cancer, has been shown to play a crucial role in the acquisition o f genomic instability. We examined 44 lung cancer specimens to search for m utations in the CHK1 and CHK2 genes, which have been suggested to play role s in regulating p53 after DNA damage. We found that the CHK2 gene was somat ically mutated in lung cancer in vivo, although at a Low frequency, and tha t a previously undescribed shorter isoform of CHK1 was expressed preferenti ally in small cell lung cancer in a tumor-predominant manner. Additional st udies are warranted to investigate the functional significance of these cha nges as well as the potential involvement of other components in this impor tant pathway to maintain genomic stability.