Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development

Deciphering clonality in aneuploid breast tumors using SNP array and sequencing data

Intra-tumor heterogeneity concerns the existence of genetically different subclones within the same tumor. Single sample quantification of heterogeneity relies on precise determination of chromosomal copy numbers throughout the genome, and an assessment of whether identified mutation variant allele fractions match clonal or subclonal copy numbers. We discuss these issues using data from SNP arrays, whole exome sequencing and pathologist purity estimates on several breast cancers characterized by ERBB2 amplification. We show that chromosomal copy numbers can only be estimated from SNP array signals or sequencing depths for subclonal tumor samples with simple subclonal architectures under certain assumptions.status: publishe

Deciphering clonality in aneuploid breast tumors using SNP array and sequencing data.

Intra-tumor heterogeneity concerns the existence of genetically different subclones within the same tumor. Single sample quantification of heterogeneity relies on precise determination of chromosomal copy numbers throughout the genome, and an assessment of whether identified mutation variant allele fractions match clonal or subclonal copy numbers. We discuss these issues using data from SNP arrays, whole exome sequencing and pathologist purity estimates on several breast cancers characterized by ERBB2 amplification. We show that chromosomal copy numbers can only be estimated from SNP array signals or sequencing depths for subclonal tumor samples with simple subclonal architectures under certain assumptions.info:eu-repo/semantics/publishe