The Impact of Comprehensive Panel NGS Testing and Cascade Family Screening on Early Diagnosis of Prostate Cancer and...

With the expansion of next-generation sequencing (NGS)-based hereditary cancer panels, this study aimed to: (i) identify non-BRCA predisposition genes in an index case with three different primary cancers; (ii) demonstrate the clinical utility of cascade testing via comprehensive panel NGS testing for early cancer detection in asymptomatic relatives; (iii) discuss the potential association between a co-segregating MITF variant and a family history of recurrent meningioma; and (iv) provide a practical management framework for Multilocus Inherited Neoplasia Allele Syndrome (MINAS) in the context of dual ATM+MITF carriership.

Index patient and family members who have a history of cancer with a familial cancer pedigree were evaluated using a multigene NGS approach. Targeted sequencing was performed on the MGI DNBSEQ-G400 platform using the Twist Bioscience Hereditary Cancer Panel.

A germline ATM variant was identified in the index case, and ATM carrier status was confirmed in his two sons. During cascade screening, early-stage colon cancer was detected on colonoscopy in one son, while prostate cancer was diagnosed in the other. MITF carrier status was identified in three family members; among them, the index patient's sister and one nephew had a history of meningioma, and the nephew was also shown to be an ATM carrier. A history of meningioma was also present in another family member with an MITF variant.

Large-panel NGS testing in cancer patients is transforming family-based risk management by enabling the identification of homologous recombination repair (HRR) genes (including ATM) beyond BRCA1/2. Cascade testing via comprehensive NGS provides tangible clinical benefits by detecting malignancies early in clinically silent carriers.