Evidence map›Paper›PMID 30029640›Full record

ArticleBMC cancer2018

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

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 and 5 more

Abstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

M B MogensenDepartment of Oncology, Section 5073, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark. marie.benzon.mogensen@regionh.dk.
M RossingCenter for Genomic Medicine, Rigshospitalet,Copenhagen University Hospital, 2100, Copenhagen, Denmark.
O ØstrupCenter for Genomic Medicine, Rigshospitalet,Copenhagen University Hospital, 2100, Copenhagen, Denmark.
P N LarsenDepartment of Surgical Gastroenterology and Transplantation, Rigshospitalet,Copenhagen University Hospital, 2100, Copenhagen, Denmark.
P J Heiberg EngelDepartment of Pathology, Roskilde Hospital, Copenhagen University Hospital, 4000, Roskilde, Denmark.
L N JørgensenDigestive Disease Center, Bispebjerg Hospital, Copenhagen University Hospital, 2400, Copenhagen, Denmark.
E V HogdallDepartment of Pathology, Herlev Hospital, Copenhagen University Hospital, 2730, Herlev, Denmark.
J EriksenDepartment of Surgical Pathology, Zealand University Hospital, Slagelse Hospital, 4200, Slagelse, Denmark.
P IbsenDepartment of Pathology, Hvidovre Hospital, Copenhagen University Hospital, Copenhagen, 2650, Hvidovre, Denmark.
P JessDepartment of Surgical Gastroenterology, Roskilde Hospital, Copenhagen University Hospital, 4000, Roskilde, Denmark.
M GrauslundDepartment of Pathology, Rigshospitalet,Copenhagen University Hospital, 2100, Copenhagen, Denmark.
H J NielsenDepartment of Surgical Gastroenterology, Hvidovre Hospital, Copenhagen University Hospital, 2650, Hvidovre, Denmark.
F C NielsenCenter for Genomic Medicine, Rigshospitalet,Copenhagen University Hospital, 2100, Copenhagen, Denmark.
B VainerDepartment of Pathology, Rigshospitalet,Copenhagen University Hospital, 2100, Copenhagen, Denmark.
K OsterlindDepartment of Oncology, Section 5073, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Funding

The Danish Council for Strategic Research 10-092308
6 · The paper itself

Abstract

backgroundColorectal 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.

methodsFresh-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.

resultsShared 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.

conclusionThe 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.

Indexed as

AdultAgedAged, 80 and overColorectal NeoplasmsDNA Copy Number VariationsExome SequencingFemaleGenes, APCGenomicsHumansLiver NeoplasmsMaleMiddle AgedMutationProto-Oncogene Proteins p21(ras)KRAS protein, humanProto-Oncogene Proteins p21(ras)Colorectal cancerConcordanceHeterogeneityMetastatic cancer

Identifiers

PMID30029640
PMCPMC6053835

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.