Comprehensive whole-exome and transcriptome profiling to identify actionable alterations associated with response to PARP inhibitors in breast cancer

Autor: Susan M. Dombrowski, Sameer S. Udhane, Gargi D. Basu, David W. Hall, Jess W. Hoag, Fadel S. Alyaqoub, Pawan Noel, Szabolcs Szelinger, Min Wang, Audrey A. Ozols, Janine R. LoBello, Snehal Govind Thakkar, Frederick L. Baehner, Joyce O'Shaughnessy
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:1096-1096
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2022.40.16_suppl.1096
Popis: 1096 Background: The use of targeted therapies identified using genetic and genomic approaches is now routine in breast cancer (BC). In this clinical lab experience study the frequency of actionable somatic alterations in DNA repair pathway genes associated with the use of PARP inhibitors (PARPi) is described. Methods: BC samples were sequenced with the Oncomap ExTra assay, which uses whole-exome DNA sequencing with germline subtraction to detect somatic single base substitutions, indels, and copy number alterations, and RNA sequencing to detect gene fusions. Clinically actionable alterations were defined as associated with FDA approved drugs or clinical trial enrollment. Here, the focus is on 49 repair genes associated with PARPi response: ARID1A, ATM, ATR, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CDK12, CHEK1/2, EPCAM, ERCC1/2/3/4/5, FANCA/C/D2/E/F/G/I/L/M, MLH1, MRE11A, MSH2/6, MUTYH, NBN, PALB2, PMS2, PPP2R2A, PTEN, RAD21/50/51/51B/51C/51D/52/54L, XRCC1/2/3. Results: Of 1103 BCs, 246 (22.3%) had mutations in repair genes; 69 (6.3%) were in BRCA1/2. Repair gene mutations were less common in HER2+ cancers (n=27, 14.3%) compared to HR+ HER2- (n=156, 23.9%) or TN cancers (n=49, 26.1%) (p+ cancers (p- germline BRCA1/2 mutated BC patients. Recent evidence suggests somatic BRCA1/2 mutations predict PARPi benefit (Tung, NM. J Clin Oncol 2020). In addition to BRCA1/2 alterations, our study also highlights the importance of alterations in other DNA repair genes associated with response to PARPi. Trials are ongoing to determine if these genes predict for PARPi benefit.[Table: see text]
Databáze: OpenAIRE
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