RET fusion signals unique NSCLC subtype

Published on December 10, 2012 at 5:15 PM · No Comments

By Joanna Lyford, Senior medwireNews Reporter

The presence of RET fusion genes in approximately 1.5% of non-small-cell lung cancer (NSCLC) defines a subset of tumors with distinct clinicopathologic features, research suggests.

The findings warrant "further clinical consideration and targeted therapy investigations," say Haiquan Chen (Fudan University Shanghai Cancer Center, China) and co-authors writing in the Journal of Clinical Oncology.

RET fusion genes - ie, the RET tyrosine kinase gene partnered with either KIF5B or CCDC6 - has recently been described in a subset of NSCLCs. To further characterize this gene, Chen et al obtained tumor samples from 936 patients with surgically resected NSCLC.

Molecular analysis identified a RET fusion gene in samples from 13 patients - 11 (1.7%) of 633 patients with adenocarcinomas and two (8.3%) of 24 patients with adenosquamous cell carcinomas.

Further study of these 13 samples revealed that nine patients had KIF5B-RET, three had CCDC6-RET, and one had a novel NCOA4-RET fusion.

Interestingly, the presence of a RET fusion gene was associated with several unique features among adenocarcinoma patients, including poorly differentiated tumors, young age, never-smoking status, solid subtype, small lesion size, N2 disease, and the presence of signet ring cells.

In terms of clinical outcomes, the median recurrence-free survival (RFS) was 20.9 months for patients with a RET fusion gene, compared with 28.4 months, 12.3 months, and 26.9 months for patients with mutations in the EGFR, KRAS, and ALK genes, respectively.

However, for patients with NSCLC or lung adenocarcinoma, there was no difference in either RFS or overall survival between patients with RET-positive and RET-negative tumors.

Chen et al note that an increasing number of gene fusions are being discovered, including most recently in solid tumors, thanks to refinements in cytogenetic techniques.

"As a receptor tyrosine-protein kinase, RET plays important roles in cell proliferation, neuronal navigation, cell migration, and cell differentiation on binding with the glial cell-derived neurotrophic factor family of ligands," they write.

"Because the growth of these tumors is strongly addicted to RET activity, suppression of RET could be a potent therapeutic strategy for patients with RET arrangements."

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