MPTevol

MPTevol reconstructs clonal evolution and metastatic seeding in multi-primary tumors from multiregion sequencing (MRS) data to infer tumor heterogeneity, metastatic routes, and dissemination timing.

Key Features:

• Multiregion Sequencing (MRS) Integration: Leverages multiregion sequencing data to compare genomic profiles across multiple tumor samples from a single patient for analysis of intrapatient heterogeneity and evolutionary trajectories.
• Clonal Evolutionary Analysis: Systematically investigates clonal dynamics by comparing genomic profiles to detect evolutionary histories and quantify metastatic history and spread patterns.
• Independent Tumorigenesis Verification: Demonstrated in a case study of a patient with triple-primary tumors and multiple metastases that all primary tumors originated independently, matching genomic characteristics of sporadic tumors.
• Metastatic Seeding Events Detection: Identified two early monoclonal seeding events to ovary and uterus and found two ovarian metastases derived from the same primary subclone that underwent whole-genome doubling, indicating metastases-to-metastases seeding under similar microenvironments.
• Early Metastasis Detection: Applies a metastasis timing model that inferred dissemination from primary tumors as small as 0.058-0.124 cm in diameter to distant organs.

Scientific Applications:

• MPT evolutionary reconstruction: Resolve clonal evolutionary history and intratumor heterogeneity in multi-primary tumors (MPTs).
• Metastatic seeding and timing inference: Infer monoclonal seeding events, metastases-to-metastases transmissions, and timing of dissemination including early dissemination estimates.
• Independent tumorigenesis assessment: Evaluate whether multiple primary tumors in a patient arose independently versus from a common origin.
• Characterization of genomic events in metastases: Detect whole-genome doubling and identify subclone origins of metastases in specific sites such as ovary and uterus.

Methodology:

Implemented in R.