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Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing

Overview of attention for article published in BMC Cancer, July 2018
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Title
Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing
Published in
BMC Cancer, July 2018
DOI 10.1186/s12885-018-4639-4
Pubmed ID
Authors

M. B. Mogensen, M. Rossing, O. Østrup, P. N. Larsen, P. J. Heiberg Engel, L. N. Jørgensen, E. V. Hogdall, J. Eriksen, P. Ibsen, P. Jess, M. Grauslund, H. J. Nielsen, F. C. Nielsen, B. Vainer, K. Osterlind

Abstract

Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Professor 4 9%
Student > Postgraduate 4 9%
Other 3 7%
Student > Master 3 7%
Researcher 3 7%
Other 9 21%
Unknown 17 40%
Readers by discipline Count As %
Medicine and Dentistry 13 30%
Biochemistry, Genetics and Molecular Biology 7 16%
Nursing and Health Professions 2 5%
Agricultural and Biological Sciences 2 5%
Business, Management and Accounting 1 2%
Other 2 5%
Unknown 16 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 July 2018.
All research outputs
#20,527,576
of 23,096,849 outputs
Outputs from BMC Cancer
#6,550
of 8,384 outputs
Outputs of similar age
#287,428
of 328,924 outputs
Outputs of similar age from BMC Cancer
#104
of 137 outputs
Altmetric has tracked 23,096,849 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,384 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 137 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.