Abstract 5307: Inferring parsimonious migration histories for metastatic cancers
| Autor: | Benjamin J. Raphael, Gryte Satas, Mohammed El-Kebir |
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| Rok vydání: | 2018 |
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| Zdroj: | Cancer Research. 78:5307-5307 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2018-5307 |
| Popis: | Recent studies have attempted to infer the pattern of cellular migrations between a primary tumor and distant metastases using phylogenetic trees constructed from somatic mutations. Several of these studies have challenged the conventional view of monoclonal seeding of a metastasis, and reported complex patterns of migration between primary tumors and metastases, including polyclonal seeding and reseeding. Most current analyses that attempt to infer migration patterns from somatic mutations rely on two key assumptions, sample homogeneity and mutation-migration concordance, that do not typically hold for cancer sequencing datasets. Consequently, standard phylogenetic analysis of mutations may result in incorrect or misleading patterns of metastasis. We introduce a computational model to evaluate migration patterns in a rigorous manner. We use this model as a basis for Metastatic And Clonal History INtegrative Analysis (MACHINA), an algorithm that jointly infers parsimonious clone trees and migration histories of metastatic cancers from DNA sequencing data. We show that MACHINA accurately recovers clone trees and migration histories on simulated data. We apply MACHINA to sequencing data from metastatic ovarian, breast, prostate and skin cancer samples. In several cases, we find simpler migration histories than previously reported, and these alter conclusions regarding metastasis-to-metastasis spread, the anatomical site of the primary tumor, or the occurrence of polyclonal seeding and reseeding in individual patients. MACHINA enables researchers to rigorously assess the validity of different migration patterns in individual patients with metastatic disease and evaluate the prevalence of different migration patterns across large cohorts of patients and tumor types. Citation Format: Mohammed El-Kebir, Gryte Satas, Benjamin J. Raphael. Inferring parsimonious migration histories for metastatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5307. |
| Databáze: | OpenAIRE |
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