Clinically actionable molecular alterations in Rb-retained small cell lung carcinoma variants
Rb‑retained small cell lung carcinoma (SCLC) can harbor clinically actionable oncogenic drivers such as KRAS G12C (responsive to sotorasib) and novel IKZF2::ERBB4 fusions, underscoring the need for routine Rb assessment and comprehensive molecular profiling in these tumors.
Small cell lung carcinoma (SCLC) is classically defined by biallelic inactivation of RB1 and TP53. However, a small subset of tumors retains Rb expression and exhibits distinct molecular features. Here, we report two Rb‑retained SCLC cases that expand the biological and therapeutic spectrum of this subgroup. Both tumors occurred in middle‑aged women, showed small‑cell morphology with some variant features, and displayed complex copy number alterations. Case 1 harbored a truncal KRAS p.G12C mutation with high‑level amplification of chromosome 11q13‑q14, including CCND1, and demonstrated a clinical response to sotorasib. Case 2 harbored a TP53 mutation, CDKN2A loss, STK11 inactivation, and a novel IKZF2::ERBB4 fusion. These findings highlight the molecular heterogeneity of Rb‑retained SCLC and demonstrate that this subgroup can harbor clinically actionable oncogenic drivers. Accordingly, routine assessment of Rb expression in SCLC, followed by comprehensive molecular profiling of Rb‑retained tumors, is warranted to uncover therapeutically relevant targets.
The study demonstrates that Rb‑retained SCLC harbor actionable alterations uncommon in classic SCLC, providing a rationale for tailored therapy and highlighting the importance of Rb immunohistochemistry and extensive genomic profiling in these rare variants.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
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