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Newly Identified HER2 Mutations in Non–Small Cell Lung Cancer Focus on Exons 18 and 19

By: Kayci Reyer
Posted: Monday, May 16, 2022

Research presented in JCO Precision Oncology identified a set of distinct, uncommon insertions and deletions within the cancer driver gene human epidermal growth factor receptor 2 (EGFR2) that may themselves act as driver mutations for lung cancer and other types of cancer in Chinese patients. Insertions and deletions in HER2 exon 18 and 19 were found to be possible progression catalysts as well as potential targets for selective therapy, according to Jianwen Qin, MD, of Tianjin Chest Hospital, China, and colleagues.

The retrospective study analyzed samples from patients with lung cancer (n = 53,591), colorectal cancer (n = 5,888), breast cancer (3,774), or urothelial carcinoma of the renal pelvis (n = 14). Targeted sequencing identified 25 insertions and deletions—17 recurrent—in HER2 exon 18 and 19 located in 0.037%, 0.034%, 0.053%, and 7.1% of lung, colorectal, breast, and urothelial cancer samples, respectively. Many patients found to have HER2 exon 18 and 19 insertions and deletions did not have other known driver mutations. However, among patients with lung cancer, mutation profiles between those carrying HER2 exon 18 and 19 insertions and deletions and known HER2 driver mutations in exon 20 and S310 were similar. Additional in silico and in vitro analyses revealed that HER2 exon 18 and 19 insertions and deletions triggered an activated genetic state that may serve as a target for tyrosine kinase inhibitor treatment.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.


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