title: Assessing matched normal and tumor pairs in next-generation sequencing studies.
abstract: Next generation sequencing technology has revolutionized the study of cancers. Through matched normal-tumor pairs, it is now possible to identify genome-wide germline and somatic mutations. The generation and analysis of the data requires rigorous quality checks and filtering, and the current analytical pipeline is constantly undergoing improvements. We noted however that in analyzing matched pairs, there is an implicit assumption that the sequenced data are matched, without any quality check such as those implemented in association studies. There are serious implications in this assumption as identification of germline and rare somatic variants depend on the normal sample being the matched pair. Using a genetics concept on measuring relatedness between individuals, we demonstrate that the matchedness of tumor pairs can be quantified and should be included as part of a quality protocol in analysis of sequenced data. Despite the mutation changes in cancer samples, matched tumor-normal pairs are still relatively similar in sequence compared to non-matched pairs. We demonstrate that the approach can be used to assess the mutation landscape between individuals.
authors: Cancer and Stem Cell Biology Program, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. liang.goh@duke-nus.edu.sg
authors: Liang
authors: L
authors: Goh
authors: Geng Bo
authors: GB
authors: Chen
authors: Ioana
authors: I
authors: Cutcutache
authors: Benjamin
authors: B
authors: Low
authors: Bin Tean
authors: BT
authors: Teh
authors: Steve
authors: S
authors: Rozen
authors: Patrick
authors: P
authors: Tan
mesh_terms: D016000:Cluster Analysis; D018095:Germ-Line Mutation; D006801:Humans; D009369:Neoplasms / Q000235:genetics*