Unique genomic and neoepitope landscapes across tumors: a study across time, tissues, and space within a single lynch syndrome patient.

Scientific Reports
Tanya N PhungMichael T Barrett

Abstract

Lynch syndrome (LS) arises in patients with pathogenic germline variants in DNA mismatch repair genes. LS is the most common inherited cancer predisposition condition and confers an elevated lifetime risk of multiple cancers notably colorectal and endometrial carcinomas. A distinguishing feature of LS associated tumors is accumulation of variants targeting microsatellite repeats and the potential for high tumor specific neoepitope levels. Recurrent somatic variants targeting a small subset of genes have been identified in tumors with microsatellite instability. Notably these include frameshifts that can activate immune responses and provide vaccine targets to affect the lifetime cancer risk associated with LS. However the presence and persistence of targeted neoepitopes across multiple tumors in single LS patients has not been rigorously studied. Here we profiled the genomic landscapes of five distinct treatment naïve tumors, a papillary transitional cell renal cell carcinoma, a duodenal carcinoma, two metachronous colorectal carcinomas, and multi-regional sampling in a triple-negative breast tumor, arising in a LS patient over 10 years. Our analyses suggest each tumor evolves a unique complement of variants and that vaccines b...Continue Reading

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Methods Mentioned

BETA
chromosomal aberrations
PCR
exome sequencing
biopsies
biopsy
flow cytometry
dissection
Feature Extraction

Software Mentioned

pvacseq
bwa
XYalign
Illumina
mem
EpitopeHunter
MultiCycle
VarScan
RTA
Agilent Feature Extraction

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