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CRC Resistance to EGFR-Targeting Treatments Linked to Baseline, Acquired ARID1A Mutations

In Nature Communications, a team from Genentech, the University of Southern California Comprehensive Cancer Center, and elsewhere describe treatment resistance-related mutations in the epigenetic regulator gene ARID1A in colorectal cancer (CRC). The investigators turned to targeted circulating cell-free DNA sequencing to assess blood samples collected over time from up to 354 individuals with metastatic CRC before, during, and after treatment with chemotherapy in combination with the anti-EGFR treatment cetuximab or the anti-VEGF treatment bevacizumab. Their results suggest anti-EGFR treatment can select for ARID1A mutations in CRC — an effect not detected after anti-VEGF treatment. Along with these acquired mutations, the presence of pre-treatment mutations in ARID1A tended to coincide with poorer outcomes after anti-EGFR treatment. "We find that, ARID1A and EGFR-pathway genetic alterations are mutually exclusive across lung and colorectal cancers, further supporting a functional connection between these pathways," the authors report. "Our results not only suggest that ARID1A could be potentially used as a predictive biomarker for cetuximab treatment decisions but also provide a rationale for exploring therapeutic MAPK inhibition in an unexpected but genetically defined segment of CRC patients."

The Scan

ChatGPT Does As Well As Humans Answering Genetics Questions, Study Finds

Researchers in the European Journal of Human Genetics had ChatGPT answer genetics-related questions, finding it was about 68 percent accurate, but sometimes gave different answers to the same question.

Sequencing Analysis Examines Gene Regulatory Networks of Honeybee Soldier, Forager Brains

Researchers in Nature Ecology & Evolution find structural network differences between soldiers and foragers, suggesting bees can take on either role.

Analysis of Ashkenazi Jewish Cohort Uncovers New Genetic Loci Linked to Alzheimer's Disease

The study in Alzheimer's & Dementia highlighted known genes, but also novel ones with biological ties to Alzheimer's disease.

Tara Pacific Expedition Project Team Finds High Diversity Within Coral Reef Microbiome

In papers appearing in Nature Communications and elsewhere, the team reports on findings from the two-year excursion examining coral reefs.