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Eur J Cancer. 2015 May;51(7):791-9. doi: 10.1016/j.ejca.2015.02.012. Epub 2015 Mar 18.

Comparative analysis of primary tumour and matched metastases in colorectal cancer patients: evaluation of concordance between genomic and transcriptional profiles.

Author information

1
Oncologie Hématologie, Hôpitaux de Chartres, Chartres Le Coudray, France; INSERM U981, Gustave Roussy, Villejuif Grand Paris, France.
2
INSERM U981, Gustave Roussy, Villejuif Grand Paris, France.
3
Foundation Medicine, Cambridge, MA, USA.
4
Unité de Génomique Fonctionnelle, Gustave Roussy, Villejuif Grand Paris, France.
5
Groupe Hospitalier Pitié Salpêtrière, Paris, France.
6
INSERM U981, Gustave Roussy, Villejuif Grand Paris, France. Electronic address: jean-charles.soria@gustaveroussy.fr.

Abstract

PURPOSE:

Focal and temporal tumour heterogeneity can represent a major challenge for biology-guided therapies. This study proposes to investigative molecular discrepancies between primary colorectal cancer (CRC) samples and matched metastases.

EXPERIMENTAL DESIGN:

Surgical samples from primary and matched metastatic tissues from 13 CRC patients along with their adjacent normal tissue were evaluated. A mutational analysis was performed using a targeted Next Generation Sequencing assay (Foundation Medicine) with a focus on known recurrent somatic mutations as surrogate of key oncogenic events. Gene expression analysis was also performed to investigate transcriptional discrepancies.

RESULTS:

Among the 26 samples, 191 mutations were identified including mutations in APC (13 pts), TP53 (11 pts), and KRAS (7 pts). Global concordance rate for mutations was 78% between primary and metastatic tumours and raised to 90% for 12 known recurrent mutations in CRC. Differential gene expression analysis revealed a low number of significantly variant transcripts between primary and metastatic tumours once the tissue effect was taken into account. Only two pathways (ST_ADRENERGIC, PID_REELINPATHWAY) were differentially up-regulated in metastases among 17 variant pathways. A common profile in primary and metastatic tumours revealed conserved pathways mostly involved in cell cycle regulation. Only two pathways were significantly down regulated compared to normal control, including regulation of autophagy (KEGG_REGULATION_OF_AUTOPHAGY).

CONCLUSION:

These results suggest that profiles of primary tumour can identify key alterations present in matched CRC metastases at first metastatic progression. Gene expression analysis identified mainly conserved pathways between primary tumour and matched liver metastases.

KEYWORDS:

Colorectal cancer; Discrepancies; Metastasis; Primary tumour; Recurrent mutations

PMID:
25797355
DOI:
10.1016/j.ejca.2015.02.012
[Indexed for MEDLINE]

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