What question did this study set out to answer?

To investigate the characteristics and therapeutic potential of the rare EGFR L833V/H835L cis mutation in non-small cell lung cancer.

April 5, 2026

Abstract 7736: Rare EGFR cis compound L833V/H835L mutation in non-small cell lung cancer is oncogenic and a therapeutic target of EGFR tyrosine kinase inhibitors

Puntos clave

To investigate the characteristics and therapeutic potential of the rare EGFR L833V/H835L cis mutation in non-small cell lung cancer.
Retrospective review of clinicopathologic features in NSCLC patients with EGFR mutations.
Identification of 8 patients with the L833V/H835L mutation from a population of 3835.
Functional analyses using in vitro (NIH-3T3 and Ba/F3 cells) and in vivo models.
Structural modeling to assess kinase activity.
Four patients treated with EGFR TKIs achieved a median progression-free survival of 13 months.
The L833V/H835L mutant demonstrated oncogenic potential including cell transformation and growth independence.
Increased kinase activity was noted in structural modeling, confirming oncogenic properties.

Resumen

Abstract Non-small cell lung cancer (NSCLC) with EGFR L833V/H835L in cis mutation remains poorly understood. We retrospectively reviewed the clinicopathologic features NSCLC with either EGFR L833V or H835L mutation. The study population includes NSCLC patients (n=3835) at Samsung Medical Center, Seoul, Korea. A total of 8 patients with EGFR L833V/H835L in cis mutation were identified. Poorly differentiated histology (either micropapillary or solid patterns) presented in 4 of 5 resected cases. Four patients received EGFR tyrosine kinase inhibitors (TKIs) and achieved a median progression-free survival of 13 months. The oncogenic and therapeutic properties of the mutation were investigated through a combination of functional and biochemical analyses, utilizing both in vitro and in vivo models, and structural modeling. The L833V/H835L mutant exhibited oncogenic potential, transforming NIH-3T3 cells and promoting IL3-independent growth in Ba/F3 cells. Furthermore, EGFR TKIs effectively suppressed the mutant's oncogenic activity in both in vitro and in vivo studies. These phenomena are further supported by its increased kinase activity in structural modeling. Although rare, EGFR L833V/H835L in cis mutation, represents a biologically oncogenic and clinically actionable variant in NSCLC. Citation Format: Yo Han Jeon, Ahjin Lim, Myung Kyung Choi, Hee Seong Choi, Yurimi Lee, Hyunju Song, Hyun-Soo Cho, Jeonghee Cho, Yoon-La Choi. Rare EGFR cis compound L833V/H835L mutation in non-small cell lung cancer is oncogenic and a therapeutic target of EGFR tyrosine kinase inhibitors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7736.

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