Atypical Droplet Digital Polymerase Chain Reaction Patterns That Indicate Uncommon but Clinically Actionable EGFR Mutations in Lung Cancer.

Autor:	Lechner A; From the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Lechner, Rai, Rojas-Rudilla, Sholl, Dong).; the University of Missouri School of Medicine, Columbia (Lechner)., Rai A; From the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Lechner, Rai, Rojas-Rudilla, Sholl, Dong)., Rojas-Rudilla V; From the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Lechner, Rai, Rojas-Rudilla, Sholl, Dong)., Kuang Y; the Belfer Center for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts(Kuang).; the Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts(Kuang, Paweletz)., Paweletz CP; the Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts(Kuang, Paweletz)., Sholl LM; From the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Lechner, Rai, Rojas-Rudilla, Sholl, Dong)., Dong F; From the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Lechner, Rai, Rojas-Rudilla, Sholl, Dong).
Jazyk:	angličtina
Zdroj:	Archives of pathology & laboratory medicine [Arch Pathol Lab Med] 2024 May 01; Vol. 148 (5), pp. 553-558.
DOI:	10.5858/arpa.2023-0088-OA
Abstrakt:	Context: Droplet digital polymerase chain reaction (ddPCR) is a sensitive method to detect common pathogenic EGFR mutations in non-small cell lung cancer. Although targeted assays have not been specifically designed to detect them, uncommon EGFR mutations have been linked to response to targeted therapy. Objective: To describe atypical ddPCR patterns that correspond to uncommon but clinically actionable EGFR mutations. Design: A cohort of 1134 consecutive non-small cell lung cancers that underwent targeted next-generation sequencing was reviewed. Uncommon EGFR mutations involving probe binding sites were evaluated by ddPCR. Results: Two hundred fifty-five of 1134 cancers (22.5%) harbored pathogenic EGFR mutations. One hundred eighty-six of 255 (72.9%) had canonical EGFR exon 19 deletion or exon 21 p.L858R variants designed for detection by ddPCR. An additional 25 of 255 cases (9.8%) had uncommon EGFR mutations within the probe-binding site, including 1 case with concurrent uncommon mutations in both exon 19 and exon 21. These mutations included uncommon EGFR exon 19 deletions (n = 6), EGFR exon 19 substitutions p.L747P (n = 3) and p.L747A (n = 1), dinucleotide substitutions leading to EGFR p.L858R (n = 5), EGFR exon 21 substitutions p.K860I (n = 1) and p.L861Q (n = 9), and EGFR p.[L858R;K860I] (n = 1). Droplet digital polymerase chain reaction generated atypical but reproducible signal for each of these uncommon variants. Conclusions: Droplet digital polymerase chain reaction analysis of uncommon pathogenic EGFR variants can yield unique and reproducible results. Recognition of atypical patterns in EGFR ddPCR testing can prompt confirmatory molecular testing and aid appropriate targeted therapy selection for patients with non-small cell lung cancer. Competing Interests: The authors have no relevant financial interest in the products or companies described in this article. (© 2024 College of American Pathologists.)
Databáze:	MEDLINE
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