Accession PRJCA000625
Title Multi-omics analysis in primary cell cultures reveals the genomic basis of phenotypic diversity within tumors
Relevance Medical
Data Types Whole genome sequencing
Transcriptome or Gene expression
Organisms Homo sapiens
Description To uncover the functionally essential variations related to tumorigenesis and tumor progression from large amount of cancer genomics data is still challenging due to the genetic diversity between patients, and extensive inter- and intra-tumor heterogeneity at the genomic, epigenomic, and transcription levels and consequently phenotypic diversity. Multiple primary cultures derived from phenotypically distinct subpopulations within a single patient may not only represent the diversity and heterogeneity of tumor cells such as metastasis and drug-resistant tumors occurring the patient, but also narrow the analysis in the genomic basis of phenotypic diversity down to the relatively small number of variations between subpopulations with the same genetic background. Performing next-generation sequencing, we identified single nucleotide variations(SNVs), copy number, DNA methylation and gene expression among 4 primary cell cultures from primary and recurrent tumors in a hepatocellular carcinoma patient. We observed the discrepancy between the phylogenetic relationships revealed by SNVs and transcriptional profiles in the 4 cell cultures. The differences in gene expression, which indicated the distinct cellular characteristics and tumorigenic capability in one of the two recurrent cell clones, were correlated to the copy number alterations (CNAs) and DNA methylation variation in gene body and confirmed by the characterization of cellular phenotype. The multi-omics analysis in heterogeneous clones derived from an individual revealed that CNAs and epigenomic changes, rather than SNVs, dominantly contribute to the phenotypic diversity among subpopulations in tumors, which shed light on developing new cancer diagnosis and treatment strategies based on gene dosage change and epigenetic modification.
Sample scope primary culture cells
Release date 2018-03-06
Submitter Zuyu    Yang  (
Organization Beijing Institute of Genomics, Chinese Academy of Sciences
Submission date 2017-11-07

Project Data

Resource name Description
BioSample (6) -
SAMC018839 TIL
SAMC018838 Rb
SAMC018837 Pb
SAMC018835 Pa
SAMC018840 others
SAMC018836 Ra
GSA (1) -
CRA000636 Multi-omics sequencing of primary cell cultures