Jason Starr, DO, medical oncologist, the Department of Internal Medicine, the Mayo Clinic, discusses the characterization of 

Investigators conducted a real-world study of a large cohort of patients with colorectal cancer (CRC) to further examine the association between 

 mutations and susceptibility to immunotherapy. Data were pooled from 9,136 patients. Of these patients, 217 harbored 

 mutations, including 203 patients with 

mutations, and 1 patient with both. Although germline 

 mutations are a possibility in CRC, no instances of these germline mutations were observed in this study. 

Once investigators identified patients with 

 mutations, they focused on classifying the alteration types, such as frameshift mutations, point mutations, or copy number alterations. Notably, 58.5% of 

 copy number loss, where the gene was not being transcribed, leading to instability of the DNA, Starr notes.

Historically, patients with microsatellite instability–high (MSI-H) CRC benefit from immunotherapy. However, among evaluable patients with 

 wild-type disease (n = 8865), 6.1% had MSI-H disease, and only 1.8% of patients with 

 mutations were MSI-H. The mechanism of the immunotherapy working is not mismatch repair deficiency or MSI-H in the majority of patients; rather, this hypermutated genotype is creating neoantigens that stimulate the immune system, Starr says.

 mutations had a high tumor mutational burden, defined as greater than 10 mut/Mb. Among patients with 

 wild-type tumors, 9.9% had a high tumor mutational burden. These findings suggested that 

 mutations are not synonymous with a high tumor mutational burden, which was disappointing for investigators, who hoped to identify more patients that could benefit from immunotherapy, Starr concludes.

Videos

Jason Starr, DO, discusses the characterization of POLE/POLD1 mutations in colorectal adenocarcinoma.

Jason Starr, DO

Articles

Dr. Starr on the Characterization of POLE/POLD1 Mutations in Colorectal Adenocarcinoma