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Investigation of the genes for RET and its ligand complex, GDNF/GFRα‐1, in small cell lung carcinoma
Author(s) -
Mulligan Lois M.,
Timmer Tineke,
Ivanchuk Stacey M.,
Campling Barbara G.,
Young Leah C.,
Rabbitts Pamela H.,
Sundaresan Vasi,
Hofstra Robert M. W.,
Eng Charis
Publication year - 1998
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199804)21:4<326::aid-gcc6>3.0.co;2-0
Subject(s) - glial cell line derived neurotrophic factor , multiple endocrine neoplasia type 2 , cancer research , proto oncogene proteins c ret , biology , receptor tyrosine kinase , carcinogenesis , pheochromocytoma , small cell lung carcinoma , mutation , tyrosine kinase , neurotrophic factors , carcinoma , receptor , endocrinology , gene , small cell carcinoma , germline mutation , genetics
RET is a receptor tyrosine kinase expressed in neuroendocrine cells and in tumors of these cell types. RET activation may be mediated by a ligand complex comprising glial cell line‐derived neurotrophic factor (GDNF) and GDNF family receptor alpha‐1 (GFRα‐1). Activating RET mutations are found in the inherited cancer syndrome multiple endocrine neoplasia type 2 and in a subset of the related sporadic tumors, medullary 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 carcinoma (SCLC). To determine whether RET mutations contribute to the pathogenesis of SCLC, we examined a panel of 54 SCLC cell lines. No mutations were identified in RET exons 10, 11, 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 of its ligand complex GDNF and GFRα‐1 , in 21 SCLC lines by using RT‐PCR. Although we found no consistent pattern of expression for these three genes, RET was expressed in 57% of SCLC lines. Thus, although RET mutations appear unlikely to be an important step in the tumorigenesis of SCLC, the frequent expression of this gene suggests that RET may have a mitogenic role in a subset of SCLC cell lines. Genes Chromosomes Cancer 21:326–332, 1998. © 1998 Wiley‐Liss, Inc.