Advancing Cancer Care Through Clinical Whole Genome Sequencing Clinical Significance and the Role of Genetic Counseling
Faculty Mentor
Cora N Sternberg and Monika Zak
Area of Research
Genetic Counseling, Whole Genome Sequencing
Major
Genetic Counseling
Description
INTRODUCTION: Whole genome sequencing (WGS) enables simultaneous detection of somatic mutations, copy number alterations, structural variants, tumor microenvironment biomarkers, and germline variants, all within a single unified assay, a diagnostic comprehensiveness that no targeted gene panel, whether somatic or germline, can individually deliver. Despite its potential, the clinical use of WGS remains limited by challenges such as complex data interpretation, inconsistent access to genetic counseling (GC), and gaps in documenting secondary and hereditary findings. This study assesses the clinical usefulness of WGS in a real-world oncology group and measures how genetic counseling contributes to interpreting genomic results and managing patients.
METHOD: We conducted a retrospective analysis of 70 patients with confirmed cancer diagnoses who underwent clinical WGS at the New York Genome Center (NYGC) as part of their oncologic care at Weill Cornell Medicine. Electronic health records were reviewed to extract WGS reports, prior genomic testing results, treatment modifications, clinical trial eligibility, germline findings, and genetic counseling referrals. Key variables included diagnosis, age, sex, race/ethnicity, vital status, somatic and germline alterations, tumor mutational burden (TMB), microsatellite instability (MSI), structural variants, and transcriptome alterations. Findings were categorized by clinical actionability tier and cross-referenced against standard-of-care panel results where available.
RESULTS: WGS was successfully completed in 67 of 70 patients (95.7%) across eight tumor groups. Clinically significant findings were identified in 66 patients (98.5%), including eligibility for clinical trials in 42 (62.7%), biological or prognostic insights in 21 (31.3%), and germline variants of hereditary importance in 18 (26.9%). Genetic counseling visits were documented in 26 patients (38.8%). Critical documentation gaps were found in three cases, including one patient with a pathogenic germline SDHC variant who lacked a recorded GC referral. WGS proved superior to panels by detecting oncogenic fusions, rescuing specimens that panels failed, and clearly differentiating germline and somatic variants.
DISCUSSION/CONCLUSION: These results support WGS as a first-line precision oncology test and highlight the need for standardized GC protocols to ensure equitable translation of genomic information into clinical care.
Advancing Cancer Care Through Clinical Whole Genome Sequencing Clinical Significance and the Role of Genetic Counseling
INTRODUCTION: Whole genome sequencing (WGS) enables simultaneous detection of somatic mutations, copy number alterations, structural variants, tumor microenvironment biomarkers, and germline variants, all within a single unified assay, a diagnostic comprehensiveness that no targeted gene panel, whether somatic or germline, can individually deliver. Despite its potential, the clinical use of WGS remains limited by challenges such as complex data interpretation, inconsistent access to genetic counseling (GC), and gaps in documenting secondary and hereditary findings. This study assesses the clinical usefulness of WGS in a real-world oncology group and measures how genetic counseling contributes to interpreting genomic results and managing patients.
METHOD: We conducted a retrospective analysis of 70 patients with confirmed cancer diagnoses who underwent clinical WGS at the New York Genome Center (NYGC) as part of their oncologic care at Weill Cornell Medicine. Electronic health records were reviewed to extract WGS reports, prior genomic testing results, treatment modifications, clinical trial eligibility, germline findings, and genetic counseling referrals. Key variables included diagnosis, age, sex, race/ethnicity, vital status, somatic and germline alterations, tumor mutational burden (TMB), microsatellite instability (MSI), structural variants, and transcriptome alterations. Findings were categorized by clinical actionability tier and cross-referenced against standard-of-care panel results where available.
RESULTS: WGS was successfully completed in 67 of 70 patients (95.7%) across eight tumor groups. Clinically significant findings were identified in 66 patients (98.5%), including eligibility for clinical trials in 42 (62.7%), biological or prognostic insights in 21 (31.3%), and germline variants of hereditary importance in 18 (26.9%). Genetic counseling visits were documented in 26 patients (38.8%). Critical documentation gaps were found in three cases, including one patient with a pathogenic germline SDHC variant who lacked a recorded GC referral. WGS proved superior to panels by detecting oncogenic fusions, rescuing specimens that panels failed, and clearly differentiating germline and somatic variants.
DISCUSSION/CONCLUSION: These results support WGS as a first-line precision oncology test and highlight the need for standardized GC protocols to ensure equitable translation of genomic information into clinical care.