Study Gives a Better Understanding of ARID1A Mutations in Colorectal Cancer

A component of the SWI/SNF chromatin remodeling complex, AT-rich interactive domain 1A (ARID1A), regulates gene expression. Data on the characteristics and associated clinicopathologic features of ARID1A in colorectal cancer (CRC) are limited, even though its mutations are reported in a variety of other cancers. In study findings presented at the 2018 American Society of Clinical Oncology Annual Meeting (http://abstracts.asco.org/214/AbstView_214_216871.html), researchers explained an increased understanding of the ARID1A mutation in CRC.

Researchers gathered data on patients with CRC from the Cancer Genome Atlas (TCGA), Nurses’ Health Study and Health Professionals’ Follow-Up Study (NHS/HPFS), AACR Project GENIE, and MD Anderson Cancer Center databases. All identified patients had tumors that underwent comprehensive genomic profiling.

Of the 3,127 identified patients, 196 (6.2%) had a mutation in ARID1A, and 249 mutations in ARID1A were identified across all datasets. Unlike other mutations in other genes, the ARID1A mutations were more likely to be frameshift mutation (when a protein is drastically altered because an insertion or deletion) or nonsense mutation (a genetic mutation in a DNA sequence that results in a shorter, unfinished protein product) (64.0% versus 9.1%, respectively; OR = 7.0, 95% CI = 5.6–8.7; p < 0.001).

According to the study results, the majority were considered clonal by allele frequency (defined as more than 25%). Ten recurrent (hot spot) regions were found, and the ARID1A mutations were associated with MSI-H status (OR = 8.1, 95% CI = 4.4–14.8; p < 0.001), with PIK3CA mutations (OR = 2.8, 95% CI = 2.1–3.9; p < 0.001), and BRAF mutations (OR = 3.1, 95% CI = 2.2–4.4; p < 0.001). However, an opposite correlation was shown with the TP53 mutations (OR = 0.5, 95% CI = 0.4–0.7; p < .001).

In early stages (OR = 1.83, 95% CI = 1.09–3.07; p = 0.019) and right-sided tumors (OR = 1.66, 95% CI = 1.01–2.71; p = 0.034), the ARID1A mutation was more common. However, results showed that general patient details such as age, race, and sex were not associated with ARID1A.

“ARID1A-mutated tumors demonstrate enrichment of wild-type TP53, but they are more likely to have MSI-H, PIK3CA, and BRAF mutations,” the authors concluded. “The transcriptional signature may indicate future therapeutic strategies for this subgroup.”