INVESTIGATION OF THE GENES FOR RET AND ITS LIGAND COMPLEX, GDNF GFR-ALPHA-1, IN SMALL-CELL LUNG-CARCINOMA/

RET is a receptor tyrosine kinase expressed in neuroendocrine cells an d in tumors of these cell types. RET activation may be mediated by a l igand complex comprising glial cell line-derived neurotrophic factor ( GDNF) and GDNF family receptor alpha-1 (GFR alpha-1). Activating RET m utations are found in the inherited cancer syndrome multiple endocrine neoplasia type 2 and in a subset of the related sporadic tumors, medu llary thyroid carcinoma and pheochromocytoma, both being derived from neuroendocrine tissues, In one small study, mutations were identified in another tumor with neuroendocrine features, small cell lung carcino ma (SCLC), To determine whether RET mutations contribute to the pathog enesis of SCLC, we examined a panel of 54 SCLC cell lines. No mutation s were identified in RET exons 10, I I, and 13-16, regions previously implicated in SCLC or other neuroendocrine tumors, We further examined the expression pattern of RET and the genes encoding the components o f its ligand complex GDNF and GFR alpha-1, in 21 SCLC lines by using R T-PCR. Although we found no consistent pattern of expression for these three genes, RET was expressed in 57% of SCLC lines. Thus, although R ET mutations appear unlikely to be an important step in the tumorigene sis of SCLC, the frequent expression of this gene suggests that RET ma y have a mitogenic role in a subset of SCLC cell lines, (C) 1998 Wiley -Liss, Inc.