Building research infrastructure to advance precision medicine in colorectal cancer

构建研究基础设施以推进结直肠癌精准医疗

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Abstract

BACKGROUND: Addressing critical gaps in precision medicine initiatives in colorectal cancer (CRC) requires building larger collaborative studies. METHODS: The Latino Colorectal Cancer Consortium (LC3) is a resource that harmonizes data collected in observational studies with data from individuals who identify as Hispanic/Latino with a diagnosis of primary colorectal adenocarcinoma. Data collected includes demographics, medical history, family history, and lifestyle risk factors from patient-completed surveys. Vital status, cause of death, treatment, and clinicopathological characteristics were obtained through medical chart abstraction, pathology reports, and/or linkage to state cancer registries. Blood, saliva, or normal colonic tissues were used to extract and genotype germline DNA. Tumor tissue (snap frozen or formalin-fixed paraffin-embedded) was evaluated by pathologists for diagnosis, tissue content, tumor cellularity, necrosis, immune infiltration, and additional histopathological characteristics. A centralized database with a virtual tumor repository was created to facilitate collaborative research. RESULTS: As of April 2024, LC3 assembled data from 2210 patients (diagnosed 1994 to 2023). The mean age at diagnosis was 57 (range: 19-93) years; 54.3% of participants were male, and 62.0% had been diagnosed with colon cancer. Surveys were completed by 1722 (77.8%) participants. Ongoing multi-omics profiling on up to 600 patients include: genome-wide germline genotyping, paired tumor/normal whole exome sequencing, bulk RNA-seq, T cell receptor immunosequencing, and multiplex immunofluorescence. CONCLUSIONS: This consortium fills an important gap in research infrastructure in CRC as well as improving precision medicine initiatives for all individuals.

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