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Carlos Arevalo

Carlos Arevalo

Carlos Arevalo, a senior molecular, cell and developmental biology major and minor in bioinformatics at the University of California, Santa Cruz, developed a comprehensive analysis of mutually exclusive and co-occurrent driver events in cancer to understand tumor progression and malignancy.

The characterization of driver mutations is central to understanding tumor progression and metastasis, however, the co-occurrent and mutually exclusive events in cancer cell lines and tumor biopsies is not well understood. Cancer driver genes can be classified as tumor suppressor genes (TSGs) or oncogenes (OGs) based on their role in tumor formation. I would have never imagined as an undergraduate to study driver mutations across tumor samples and cancer cell lines. While interning at the Brigham and Women’s Hospital, I learned from my mentor the theory and applications of spatial transcriptomics and single cell genomics to study rare and chronic kidney diseases. This only happens at the Broad Institute.TSGs could cause normal cells to grow out of control and become cancer, while OGs protect them from becoming cancerous. ​Studies show that both the gain of function in OGs and the loss of function in TSGs are essential for tumorigenesis. ​Many studies also demonstrate that co-occurrent and mutually exclusive driver events confer a selective growth advantage to cancerous cells and contribute to the acquisition of more mutations that result in metastatic human solid neoplasms and myeloid malignancies. Co-occurrent driver mutations and their antithetical mutational category, mutual exclusivity, are found in important biological pathways involved in cell proliferation, survival and growth, and their specificity across tumors is not well known. To address the importance of driver events for progression and metastasis, we performed a comprehensive analysis of mutually exclusive and co-occurrent driver events in the most frequently mutated driver genes in the the Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) databases. Ultimately, we characterize common mutually exclusive and co-occurrent driver events in the CCLE and TCGA and revealed that a higher number of significant co-occurrent and frequent driver mutations in both datasets might be driving tumor progression and metastasis across cancers.

 

Project: Comprehensive analysis of mutually exclusive and co-occurrent driver events in cancer

Mentors: Jamie Marshall, PhD, Greka Lab, Group leader in Kidney Disease Initiative and Human Cell Atlas