A new strategy to confirm the identity of tumour tissues using single-nucleotide polymorphisms and next-generation sequencing

Abstract

With growing cancer morbidity, forensics cases in which archived tumour tissues can be used as biological samples are increasing, and an effective method to identify the body source of tumour tissues is needed. Single nucleotide polymorphisms (SNPs) may be a promising biomarker to identify the source of tumour tissues because of their low mutation rate and small amplicon size. Next-generation sequencing techniques offers the ability to detect hundreds of SNPs in a single run. The Precision ID Identity Panel (Thermo Fisher Scientific, Waltham, MA, USA) detects 90 autosomal SNPs for individual identification and 34 lineage-informative SNPs on Y chromosome using the Ion PGM system (Thermo Fisher Scientific). In this study, we evaluated performance of the panel for individual identification of tumour tissues. One hundred and fifty pairs of tumour tissues and corresponding normal tissues were analysed. Loss of heterozygosity was detected only in tumour tissues. The identity-by-state (IBS) scoring system was adopted to identify the body source of tumour tissues. The IBS score, as well as the number of loci with 2 alleles (A₂), 1 allele (A₁) and 0 alleles (A₀) shared, were analysed within each tumour-normal pair, unrelated individual pairs, parent-offspring pairs and full-sibling pairs. According to the probability distribution, threshold of A₂ in the range of 69 to 89 could achieve accuracy > 99% in identifying the source of tumour tissues. Thus, we developed a new strategy (process and criteria) to identify the source of tumour tissues that could be used in practice.

Keywords: Forensic genetics; Identity by state (IBS); Individual identification; Next-generation sequencing (NGS); Single nucleotide polymorphism (SNP); Tumour tissues.