South Korean lung SCC genetic secrets revealed

By Lynda Williams, Senior medwireNews Reporter

Close examination of DNA taken from squamous cell carcinoma (SCC) of the lung in South Korean patients has identified a gene fusion that may be targeted by current treatments, scientists say.

The fibroblast growth factor receptor (FGFR)3–transforming acidic coiled-coil-containing protein 3 (TACC3) fusion was identified in lung SCC from six of the 104 patients assessed. All patients produced fusion transcriptions with loss of the last FGFR3 exon, leading to an increased production of FGFR3 transcripts.

FGFR antagonists are already under investigation for SCCs with mutations affecting FGFR1, FGFR2, and FGFR3, and the FGFR3–TACC3 fusion has shown susceptibility to FGFR inhibitors in other tumor types, observe Keunchil Park, from Samsung Medical Center at the Sungkyunkwan University in Seoul, and co-workers.

“Thus, it is likely that clinical trials could be expanded to test the efficacy of these agents in patients with FGFR3 fusions in lung SCC with concurrent development of companion diagnostics,” they suggest.

As published in the Journal of Clinical Oncology, whole-exome DNA sequencing revealed a high burden of mutations among the patients, with an average of 261 somatic exonic mutations per tumor.

In particular, mutations were identified at significant levels of recurrence in seven well known genes: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA.

When the researchers compared the data from the South Korean patients with that of a cohort of 178 mostly White, North American lung SCC patients, they found a similar mutation frequency of these major genes.

“[In] lung SCC, in which most of the patients had been chronically exposed to heavy doses of tobacco, the subtle genetic and inherent biologic influences seem to be largely overridden by heavy mutational burdens from exogenous carcinogens,” the team suggests.

However, the South Korean and North American patients did show significant differences in the frequency of alterations in some cell cycle regulatory genes. Compared with North American patients, South Koreans were less likely to have mutations and deletions in CDKN2A but more likely to have RB1 mutations.

Park et al conclude: “These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.”

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