2 research outputs found
DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer
Genetic heterogeneity between and within tumours is a major factor determining
cancer progression and therapy response. Here we examined DNA sequence and DNA
copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth
sequencing of 100 most frequently altered genes. In 97 samples, with primary
tumours and matched metastases from 27 patients, we observe inter-tumour
concordance for coding mutations; in contrast, gene copy numbers are highly
discordant between primary tumours and metastases as validated by fluorescent
in situ hybridization. To further investigate intra-tumour heterogeneity, we
dissected a single tumour into 68 spatially defined samples and sequenced them
separately. We identify evenly distributed coding mutations in APC and TP53 in
all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D
morpho-molecular reconstruction reveals two clusters with divergent copy
number aberrations along the proximal–distal axis indicating that DNA copy
number variations are a major source of tumour heterogeneity in CRC
DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer
Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27 patients, we observe inter-tumour concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumours and metastases as validated by fluorescent in situ hybridization. To further investigate intra-tumour heterogeneity, we dissected a single tumour into 68 spatially defined samples and sequenced them separately. We identify evenly distributed coding mutations in APC and TP53 in all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D morpho-molecular reconstruction reveals two clusters with divergent copy number aberrations along the proximal-distal axis indicating that DNA copy number variations are a major source of tumour heterogeneity in CRC