OncoAlly® Hereditary Cancer Case Study
Overview
Patient:
Male in his mid 40’s
Clinical presentation:
Pleomorphic leiomyosarcoma
Testing strategy:
Variantyx whole genome testing
Key finding:
Likely pathogenic 48 bp intronic deletion in the TP53 gene
Clinical outcome:
Diagnosis established and family testing enabled
Why OncoAlly® was the right choice
A family history significant for multiple cancers, including breast cancers and melanoma that were fatal before age 40, plus his son’s childhood rhabdomyosarcoma diagnosis and subsequent death, had prompted prior non-diagnostic panel testing of multiple family members. With the patient now presenting with his own cancer diagnosis, genetic testing was revisited.
OncoAlly® was selected because it delivers the most comprehensive genomic insight from the start while:
- Reducing time to diagnosis
- Avoiding unnecessary testing
- Supporting the highest standard of patient care
Diagnostic finding: Li-Fraumeni syndrome
Variantyx OncoAlly® hereditary cancer testing identified a heterozygous, likely pathogenic 48 bp deletion within intron 3 of the TP53 gene.
A published functional study has demonstrated that this deletion results in aberrant splicing and skipping of exon 4, removing a portion of the critical DNA binding domain 1. The deletion has been reported in a child with a history of cancers typical of Li-Fraumeni syndrome 2.
Uniform data from WGS clearly shows the intronic deletion.
References: 1. NPJ Genom Med. 2025 10(1):37. 2. J Med Genet. 2018 55(3):173-180.
Impact on clinical care
Provided an elusive diagnosis and enabled targeted follow-on screening of at-risk family members.
Variant spotlight: Intronic variants
Detection challenges
Exome and targeted panel tests focus on coding regions only, ignoring intronic sequences deeper than the +/- 10-20 bp of sequence flanking exon boundaries. This leads to critical coverage gaps and variant blind spots.
Why OncoAlly®
- Sequences and analyzes both coding and non-coding regions, eliminating coverage gaps and blind spots.
- Detects additional variant types that may occur in trans.
Additional similar cases
OncoAlly® Hereditary Cancer – SDHB deletion provides hereditary paraganglioma syndrome 4 diagnosis