Cancer Res Treat.  2017 Jan;49(1):161-167. 10.4143/crt.2015.490.

Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer

• Kim KP
• Kim JE
• Hong YS
• Ahn SM
• Chun SM
• Hong SM
• Jang SJ
• Yu CS
• Kim JC
• Kim TW

• KMID: 2367513
• DOI: http://doi.org/10.4143/crt.2015.490

Abstract

PURPOSE
Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes.
MATERIALS AND METHODS
In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients' demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review.
RESULTS
In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap.
CONCLUSION
These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

Keyword

Colorectal neoplasms; Neoplasm metastasis; Genomics

MeSH Terms

Chemistry
Colorectal Neoplasms*
Demography
Genomics
Humans
Microsatellite Instability
Neoplasm Metastasis
Retrospective Studies

Figure

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  Fig. 1. Relapse-free survival of synchronous (n=27) and metachronous (n=19) metastasis after metastasectomy.

Reference

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