Somatic TP53 variants frequently confound germ-line testing results.

ABSTRACT:

Purpose

Blood/saliva DNA is thought to represent the germ line in genetic cancer-risk assessment. Cases with pathogenic TP53 variants detected by multigene panel testing are often discordant with Li-Fraumeni syndrome, raising concern about misinterpretation of acquired aberrant clonal expansions (ACEs) with TP53 variants as germ-line results.

Methods

Pathogenic TP53 variants with abnormal next-generation sequencing metrics (e.g., decreased ratio (<25%) of mutant to wild-type allele, more than two detected alleles) were selected from a CLIA laboratory testing cohort. Alternate tissues and/or close relatives were tested to distinguish between ACE and germ-line status. Clinical data and Li-Fraumeni syndrome testing criteria were examined.

Results

Among 114,630 multigene

SUBMITTER: Weitzel JN 

PROVIDER: S-EPMC5976505 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature