Multigene panel testing (MGPT) in a large cohort of patients with colorectal cancer (CRC) revealed a high rate of clinically actionable germline variants, according to researchers. They reported this finding in JCO Precision Oncology.

“This work supports consideration of broadening germline genetic testing criteria for individuals with CRC,” the researchers wrote.

They noted that germline genetic testing is currently recommended for only a subset of patients with CRC. The aim of this study was to determine the rates of clinically actionable variants in a diverse CRC cohort.

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Researchers evaluated data from 34,244 patients with CRC who underwent MGPT of 11 or more genes between March 2015 and May 2021. Most patients were women (60.7%), and a majority were 50 years or older (68.9%). Patients were White (70.6%), Black (6.7%), Hispanic (5.6%), Asian (3.3%), Ashkenazi Jewish (1.7%), or another/unknown race (12.2%). 

Testing revealed that 14.2% of patients had at least 1 pathogenic or likely pathogenic germline variant (PGV), 11.9% of patients had clinically actionable variants, 9.1% of patients had PGVs associated with an increased risk of polyposis or CRC, and 5.7% had PGVs related to Lynch syndrome.

Patients had PGVs in MSH2 (1.6%), MSH6 (1.5%), MLH1 (1.4%), PMS2 (1.1%), and EPCAM (0.1%). An additional 3.1% of patients had other clinically actionable PGVs, most commonly in BRCA2 (0.6%), BRCA1 (0.4%), and PALB2 (0.3%).

Younger patients had higher rates of PGVs. The rate of PGVs was 25.7% in patients younger than 30 years, 17% in the 30-39 age group, 14.1% in the 40-49 age group, 15.4% in the 50-59 age group, 14.1% in the 60-69 age group, 11.3% in the 70-79 age group, and 10.1% among patients 80 years or older (P <.001).

Ashkenazi Jewish (P <.001) and Hispanic (P <.001) patients had higher rates of PGVs than White patients.

A higher number of genes in the test did not necessarily improve detection rates. A panel size of 11-20 genes resulted in a higher yield of clinically actionable CRC/polyposis genes compared with larger-sized panels (P <.001). However, larger panels were associated with a significantly higher yield of other actionable and nonactionable variants (P <.001).

“[W]e provide MGPT data from the largest cohort to date of patients with CRC, where we show that there are high rates of clinically actionable variants among patients with CRC,” the researchers concluded. “Together, these data provide evidence to support broadening of genetic testing criteria for patients with CRC.” 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Coughlin SE, Heald B, Clark DF, et al. Multigene panel testing yields high rates of clinically actionable variants among patients with colorectal cancer. JCO Prec Oncol. Published online November 12, 2022. doi:10.1200/PO.22.00517