Genome Sequencing of Undiagnosed European Patients Suspected of Hereditary Cancer: Diagnostic Yield and Clinical Impact

Multigene (WGS extended panel)

Pan-cancer WGS in European patients suspected of hereditary predisposition with prior negative WES: detection of variants in non-coding regions, deep intronic variants, structural variants and expansions undetectable by WES

Study of WGS diagnostic yield in European patients suspected of hereditary cancer predisposition with prior negative WES or gene panel. A diagnostic yield of 24% is reported in this cohort, with identification of variants undetectable by WES: variants in regulatory regions, deep intronic variants, structural variants and complex chromosomal rearrangements. These data support WGS as a second-line test in hereditary cancer predispositions after WES failure.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The 24% diagnostic yield on WES-negatives confirms the role of WGS as second-line in hereditary cancer predispositions. The spectrum of identified variants (deep intronic, SV) argues for upfront WGS in clinically suggestive syndromes without an identified WES variant.

24% diagnostic yield on WES-negatives +3; direct clinical impact (management change) +2; multicenter European cohort +2; JCO Precis Oncol +1