Related Experiment Video
Updated: Aug 5, 2026

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
A Personalized Haplotype-Resolved Near-Gapless Genome Framework for Somatic Variant Discovery in Hepatocellular
Jiazheng Lin1, Yao Xiao2,3,4, Shuangzi Luo1
1Hunan Research Center of the Basic Discipline for Cell Signaling, Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha, Hunan, China.
Abstract:
Cancer genome analysis still relies largely on universal reference genomes, which can obscure patient-specific variation in repetitive, polymorphic, and structurally complex regions. Here, we generated personalized, haplotype-resolved near-gapless assemblies from paired hepatocellular carcinoma (HCC) tumor and matched normal tissues using PacBio HiFi, ultra-long Oxford Nanopore, and Hi-C sequencing. The matched normal assembly served as a personalized reference for tumor analysis, improving read alignment relative to GRCh38, reducing multi-mapping, and achieving alignment performance comparable to T2T-CHM13. This patient-specific coordinate framework identified additional somatic small variants and structural variants, including variants missed or ambiguously represented by standard references. These assemblies also improved access to centromeric regions that are poorly captured by standard references, identifying patient-specific tumor-associated changes in assembled centromeric sequence content and repeat composition. Haplotype-resolved transcriptomic analysis identified 205 allelic pairs with allele-specific expression, including six dual protein-coding tumor-restricted candidates. Multi-omic integration further prioritized candidate regulatory alterations in MET and HSD17B2, supported by allele-dependent luciferase reporter activity. These findings support a patient-centric assembly framework that complements standard references for resolving coding and non-coding somatic alterations in HCC and provides a foundation for future cohort-scale validation.
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Cancers Originate from Somatic Mutations in a Single Cell
Cancers Originate from Somatic Mutations in a Single Cell
Histone Variants at the Centromere
