Abstract：
: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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Mamlouk S,Childs LH,Aust D,Heim D,Melching F,Oliveira C,Wolf T,Durek P,Schumacher D,Bläker H,von Winterfeld M,Gastl B,Möhr K,Menne A,Zeugner S,Redmer T,Lenze D,Tierling S,Möbs M,Weichert W,Folprecht G,Blanc E,doi
10.1038/ncomms14093subject
Has Abstractpub_date
2017-01-25 00:00:00pages
14093issn
2041-1723pii
ncomms14093journal_volume
8pub_type
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