KRAS G12Y Causing a False‐Positive KRAS G12C Result With an Indistinguishable PCR Pattern in Lung Adenocarcinoma
- 1Department of Respiratory Medicine Graduate School of Medicine, The University of Tokyo Tokyo Japan.
- 2Next-Generation Precision Medicine Development Laboratory Graduate School of Medicine, The University of Tokyo Tokyo Japan.
Abstract
KRAS G12C is an actionable alteration in non-small cell lung cancer, making accurate molecular identification essential for treatment selection. A 61-year-old man with metastatic lung adenocarcinoma showed a KRAS G12C-positive reaction on the AmoyDx Pan Lung Cancer PCR Panel (AmoyDx PLC panel). After progression on first-line chemoimmunotherapy, sotorasib was administered, but progressive disease was observed at the first radiologic assessment. Subsequent NGS-based comprehensive genomic profiling of the same pretreatment FFPE block identified KRAS G12Y (c.34_35delinsTA; variant allele frequency, 25.8%), with no sequence reads supporting KRAS G12C. This prompted suspicion of a false-positive PCR result. Repeat AmoyDx PLC panel testing reproduced the G12C-positive reaction and testing of a KRAS G12Y plasmid likewise yielded a G12C-positive reaction without additional KRAS-associated signals, confirming cross-reactivity. KRAS G12Y can therefore mimic genuine KRAS G12C in mutation-specific PCR testing and may lead to inappropriate genotype-directed therapy.
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BibTeX
@article{iwasaki2026kras,
title = {{KRAS G12Y Causing a False‐Positive KRAS G12C Result With an Indistinguishable PCR Pattern in Lung Adenocarcinoma}},
author = {Tsugumi Iwasaki and Hiroaki Ikushima and Mikako Nakamura and Yu Mikami and Kousuke Watanabe and Masanori Kawakami and Akihisa Mitani and Hidenori Kage},
journal = {Respirology case reports},
year = {2026},
month = nov,
doi = {10.1002/rcr2.70805},
url = {https://europepmc.org/article/PMC/PMC13727365},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - KRAS G12Y Causing a False‐Positive KRAS G12C Result With an Indistinguishable PCR Pattern in Lung Adenocarcinoma
AU - Tsugumi Iwasaki
AU - Hiroaki Ikushima
AU - Mikako Nakamura
AU - Yu Mikami
AU - Kousuke Watanabe
AU - Masanori Kawakami
AU - Akihisa Mitani
AU - Hidenori Kage
PY - 2026
DA - 2026/11/01
JO - Respirology case reports
DO - 10.1002/rcr2.70805
UR - https://europepmc.org/article/PMC/PMC13727365
AB - KRAS G12C is an actionable alteration in non-small cell lung cancer, making accurate molecular identification essential for treatment selection. A 61-year-old man with metastatic lung adenocarcinoma showed a KRAS G12C-positive reaction on the AmoyDx Pan Lung Cancer PCR Panel (AmoyDx PLC panel). After progression on first-line chemoimmunotherapy, sotorasib was administered, but progressive disease was observed at the first radiologic assessment. Subsequent NGS-based comprehensive genomic profiling of the same pretreatment FFPE block identified KRAS G12Y (c.34_35delinsTA; variant allele frequency, 25.8%), with no sequence reads supporting KRAS G12C. This prompted suspicion of a false-positive PCR result. Repeat AmoyDx PLC panel testing reproduced the G12C-positive reaction and testing of a KRAS G12Y plasmid likewise yielded a G12C-positive reaction without additional KRAS-associated signals, confirming cross-reactivity. KRAS G12Y can therefore mimic genuine KRAS G12C in mutation-specific PCR testing and may lead to inappropriate genotype-directed therapy.
SN - 2051-3380
ER -