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Mutant RB1 vs Wild Type RB1 in SCLC
Which tumor type responds better to chemotherapy?
Small cell lung cancer (SCLC) tumors harboring no mutation in RB1 had a poor response to chemotherapy, according to a study of 50 tumors from SCLC patients; targeted exome sequencing was obtained on 42 patients and whole-exome sequencing on 8 patients. Researchers found:
- The 2 most frequently mutated genes were TP53 (86%) and RB1 (58%).
- Other frequently mutated genes were involved in epigenetic regulation as well as the mTOR pathway.
- Low frequency, targetable mutations that were identified included RICTOR, FGFR1, KIT, PTCH1 and RET.
- In multivariate analysis, RB1 was the only significant factor in predicting response to first line chemotherapy (OR=5.58 comparing mutant RB1 to wild-type).
- Patients with mutant RB1 had better OS (11.7 vs. 9.1 months) and PFS (11.2 vs. 8.6 months) vs patients with wild-type RB1.
- About 25% of SCLC cell lines and tumor specimens expressed RB1 protein, possibly representing the subgroup with wild-type RB1.
Citation: Dowlati A, Lipka MB, McColl K, et al. Clinical correlation of extensive-stage small cell lung cancer genomics. [Published online ahead of print January 22, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw005.