A Centralized Pathology Protocol for Global Cancer Genomics: The Mutographs Project Model v1

Résumé fourni par la source

We present the pathology workflow of the Mutographs project, a multicancer genomic initiative led by the Sanger Institute and funded by Cancer Research UK, between 2017 and 2023. Mutographs aims to elucidate differences in cancer incidence through whole genome sequencing (WGS) and mutational signature analysis of over 6,000 carcinomas of the esophagus, kidney, colorectum, pancreas, head and neck, and urinary bladder collected from 27 countries. The protocol is designed by the International Agency for Research on Cancer, where centralized pathology and paired tumor-blood DNA extraction was performed. The workflow comprises four main parts. Part 1 defines handling of frozen cancer tissues for pathology and DNA extraction, followed by multi-step pathology quality evaluation and guidance through a structured five-option approach (Part 2), including macrodissection for tumors with percentage of viable tumor cells (PVTC) 3c50% (Part 3) and laser capture microdissection for certain tumor types (Part 4). Rigorous and stepwise pathology quality control led to the overall success rate of 88% in providing high-quality DNA for WGS, while 40.9% of low-quality or non-eligible tissues were excluded. PVTC was successfully enriched in 72% of 1,804 macrodissections performed. Inter-pathologist agreement to report PVTC was substantial (ICC = 0.75, CI: 0.72–0.77). This protocol provides a reproducible fully integrated pathology–molecular pipeline in challenging conditions to ensure high-quality DNA and reliable data interpretation at an unprecedented multinational scale and could be considered as a model for high-quality tissue processing in international genomics initiatives.

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