Methylation-based Liquid Biopsy Facilitates Early Detection of Small Cell Transformation in ALK-rearranged Non-Small Cell Lung Cancer.

Authors

Jinesh S Gheeya, Raj Singh, Mingjia Li, Saman Ahmadian, Konstantin Shilo, Triparna Sen, Christian Rolfo, David P Carbone, Dwight H Owen, David R Gandara

Published in

The oncologist. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a rare mechanism of resistance in anaplastic lymphoma kinase (ALK)-rearranged disease. Diagnosis is traditionally dependent on tissue biopsy, which may be limited by lesion accessibility and low disease burden. We report a case of ALK-rearranged lung adenocarcinoma that underwent small cell transformation, in which methylation-based circulating cell-free DNA (cfDNA) analysis detected a small cell lung cancer signature five months prior to tissue confirmation. Serial liquid biopsies demonstrated dynamic changes in tumor fraction and histologic composition that correlated with response to chemoradiation and continuation of ALK-directed therapy. This case highlights the potential utility of methylation-based liquid biopsy for early detection and longitudinal monitoring of histologic transformation in oncogene-driven NSCLC.

PMID:
42447248
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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