SOX2 gene potential therapeutic target for SCLC

By Lauretta Ihonor, medwireNews Reporter

Expression of the Sry-related HMG box (SOX)2 gene is higher in small-celllung cancer (SCLC) tissue samples than in non-cancerous lung tissue samples, according to findings from a genetic study.

And when expression of this gene is blocked, SCLC cell lines stop proliferating, say the authors in Nature Genetics.

This, they add, suggests that SOX2 genes facilitate SCLC progression, and the suppression of these genes may provide an unexplored avenue for SCLC treatment.

SCLC tissue samples taken from 53 individuals were compared with those from cancer-free lung tissue samples.

High levels of SOX2 amplification, defined as four or more gene copies, were identified in 27% of the SCLC samples.

In addition, SCLC samples, irrespective of level of SOX2 amplification, had higher SOX2 expression levels than cancer-free tissue samples.

Charles Rudin (Johns Hopkins University, Baltimore, Maryland, USA) and colleagues report that 22 different gene mutations were found among the SCLC samples.

Specifically, mutations of other SOX family genes and of genes coding for kinases, chromatin-modifying proteins, and G protein-coupled receptors, were identified in the SCLC samples.

A previously unidentified fusion between the RFL and MYCL1 genes was also found in SCLC cell lines. And when the MYCL1 gene was inactivated in cells with this fusion, cell proliferation declined.

Rudin and team say that this suggests that MYCL1 may contribute to SCLC development.

They add: "The recurrent nature of the RLF-MYCL1 fusion and its functional relevance provide additional opportunities for therapeutic intervention in SCLC."

Rudin et al conclude that the findings obtained from the study "provide an in-depth view of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeutic intervention."

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