2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Expanded Services Through Hereditary Cancer Panel Cascade Testing: Known Variants vs. Serendipity

Pdf Summary

This study examined a commercial laboratory cascade testing (CT) program for hereditary cancer genes. The program offered panel testing to first-, second-, and third-degree relatives of probands in whom a pathogenic variant (PV) was detected. The results showed that more than half (53%) of the relatives tested received a negative result for known familial pathogenic variants (KFPV). However, 4% of these cases were found to have a PV in a different hereditary predisposition gene. In addition to the KFPV status, 11% of the CT relatives received additional clinical information. Among these cases, 50% had new clinically actionable findings, such as a high Tyrer-Cuzick (TC) score or a different actionable PV. Some cases had low penetrant KFPV or were negative for a high-risk breast cancer KFPV. A few cases had additional findings that were not clinically actionable, such as being a carrier for a recessive condition or having a HOXB13 PV related to prostate cancer. <br /><br />The study also found that expanding access to CT beyond single-site testing and including second- and third-degree relatives led to a 10% increase in CT program use. The authors suggest that expanding access to CT and providing risk score information can enable risk-appropriate screening and prevention for hereditary cancer. The results highlight the importance of cascade testing in identifying PVs and providing valuable information for early cancer detection and prevention in at-risk relatives.

Asset Subtitle

Presenting Author - Annie Nyberg, CGC; Co-Author - Melissa K. Maisenbacher, MS, CGC; Co-Author - Silvana P. Davila, BS; Co-Author - Kelsey McQueen, BS; Co-Author - Youbao Sha, PhD, FACMG; Co-Author - Jeffrey N. Weitzel, MD; Co-Author - Katherine L. Howard, LGC, CGC, MSGC; Submitter Only - J. Bryce Ortiz, PhD;

Meta Tag

Genetic Testing

NextGen Sequencing

Polygenic risk scores

Variant Detection

Co-Author Melissa K. Maisenbacher, MS, CGC

Co-Author Silvana P. Davila, BS

Co-Author Kelsey McQueen, BS

Co-Author Youbao Sha, PhD, FACMG

Co-Author Jeffrey N. Weitzel, MD

Co-Author Katherine L. Howard, LGC, CGC, MSGC

Presenting Author Annie Nyberg, CGC

Submitter Only J. Bryce Ortiz, PhD

Keywords

commercial laboratory cascade testing

hereditary cancer genes

panel testing

probands

pathogenic variant

familial pathogenic variants

clinically actionable findings

expanding access

risk score information

early cancer detection