Abstract 504P
Background
Proteins encoded by HRR genes play crucial roles in DNA repair, maintaining genomic stability, and preventing cancer. They are essential for accurately repairing double-strand breaks and are critical for cell survival and genetic integrity. NGS of either tumor tissue or ctDNA can identify mutations in these genes. Few studies have reported regional variance of HRR gene mutation prevalence.
Methods
We analyzed the results of 473 Guardant360 TissueNext™ (GHTN) and 3,867 Guardant360® (v2.9-2.12; Guardant Health, Inc) tests conducted in AME as part of routine clinical practice for selected cancers through May 2024. These assays use tissue DNA and plasma cell-free DNA (cfDNA), respectively, to report mutations (m), amplifications (amp), and fusions in up to 84 genes. Samples were analyzed at a central laboratory. HRR-related genes included ATM, ARID1A, BRCA1, BRCA2, CHEK2, CDK12, FANCA, PALB2, and RAD51D.
Results
The success rate of tissue and cfDNA-based profiling was both 85%, yielding 403 tissue and 3,286 plasma samples with tumor DNA detected. Median turnaround times from sample receipt in the lab to results were 8 (cfDNA) and 13 (tissue) days, respectively. For GHTN: In ABC, most common alterations in National Comprehensive Cancer Network recommended (NCCNr) genes were PIK3CAm (34%), ERBB2 amp (17%), and PTENm (5%). HRRm prevalence was 21.3%, including ARID1A, ATM (5.7% each), and BRCA2 (2.7%). Common NCCNr in colorectal cancer were KRASm (45%), BRAF V600E (7%), and ERBB2 amp (3%); HRRm was 36.7%, commonly involving ARID1A (10.5%), ATM (7.9%) and BRCA2 (5.7%). For pancreatic cancer, frequent NCCNr were KRASm (80%; 1.4% G12C), BRCA1/2m (4%), and BRAF V600E (1.5%). Prevalence of HRRm was 17.4%, with ARID1A (8.6%) and ATM (2.8%) being the most common. In biliary tract cancer, prevalent NCCNr included IDH1 (12%) and ERBB2 amp (4.5%). HRRm was 32% (ARID1A [18%], ATM [6.5%], BRCA2 [2.4%]). For cfDNA: Detection rates of NCCNr and HRRm were similar to those reported for tissue-based NGS in analyzed cancer types.
Conclusions
Mutations in HRR genes can be successfully analyzed using either tumor tissue or cfDNA NGS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guardant Health AMEA, Singapore, 138567.
Funding
Guardant Health AMEA, Singapore, 138567.
Disclosure
V. Lavingia, N. Rohatgi, A. Bahl: Financial Interests, Personal, Advisory Board: Guardant Health-AMEA. S. Dawood: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Merck, Gilead; Financial Interests, Personal, Invited Speaker: Roche, MSD, BMS, Pfizer, Lilly, AstraZeneca, Caris; Financial Interests, Institutional, Research Grant: MSD, Amgen; Non-Financial Interests, Personal, Member: ASCO, ESMO. N. Sandhir, S. Olsen: Financial Interests, Personal, Full or part-time Employment: Guardant Health-AMEA. All other authors have declared no conflicts of interest.