Comparative genomic analysis of primary versus metastatic colorectal carcinomas Journal Article


Authors: Vakiani, E.; Janakiraman, M.; Shen, R.; Sinha, R.; Zeng, Z.; Shia, J.; Cercek, A.; Kemeny, N.; D'Angelica, M.; Viale, A.; Heguy, A.; Paty, P.; Chan, T. A.; Saltz, L. B.; Weiser, M.; Solit, D. B.
Article Title: Comparative genomic analysis of primary versus metastatic colorectal carcinomas
Abstract: Purpose: To compare the mutational and copy number profiles of primary and metastatic colorectal carcinomas (CRCs) using both unpaired and paired samples derived from primary and metastatic disease sites. Patients and Methods: We performed a multiplatform genomic analysis of 736 fresh frozen CRC tumors from 613 patients. The cohort included 84 patients in whom tumor tissue from both primary and metastatic sites was available and 31 patients with pairs of metastases. Tumors were analyzed for mutations in the KRAS, NRAS, BRAF, PIK3CA, and TP53 genes, with discordant results between paired samples further investigated by analyzing formalin-fixed, paraffin-embedded tissue and/or by 454 sequencing. Copy number aberrations in primary tumors and matched metastases were analyzed by comparative genomic hybridization (CGH). Results: TP53 mutations were more frequent in metastatic versus primary tumors (53.1% v 30.3%, respectively; P < .001), whereas BRAF mutations were significantly less frequent (1.9% v 7.7%, respectively; P = .01). The mutational status of the matched pairs was highly concordant (>90% concordance for all five genes). Clonality analysis of array CGH data suggested that multiple CRC primary tumors or treatment-associated effects were likely etiologies for mutational and/or copy number profile differences between primary tumors and metastases. Conclusion: For determining RAS, BRAF, and PIK3CA mutational status, genotyping of the primary CRC is sufficient for most patients. Biopsy of a metastatic site should be considered in patients with a history of multiple primary carcinomas and in the case of TP53 for patients who have undergone interval treatment with radiation or cytotoxic chemotherapies. © 2012 by American Society of Clinical Oncology.
Keywords: controlled study; human tissue; primary tumor; gene sequence; major clinical study; mutation; histopathology; gene; metastasis; gene expression profiling; mutational analysis; phosphatidylinositol 3 kinase; protein p53; colorectal carcinoma; colorectal neoplasms; cancer tissue; oncogene k ras; gene dosage; k ras protein; comparative genomic hybridization; b raf kinase; pik3ca gene; proto-oncogene proteins b-raf; genes, p53; braf gene; dna copy number variations; oncogene n ras; kras gene; nras gene; tp53 gene
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 24
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-08-20
Start Page: 2956
End Page: 2962
Language: English
DOI: 10.1200/jco.2011.38.2994
PROVIDER: scopus
PMCID: PMC3417049
PUBMED: 22665543
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 1 October 2012" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Adriana Heguy
    85 Heguy
  2. Timothy Chan
    214 Chan
  3. Leonard B Saltz
    580 Saltz
  4. Philip B Paty
    364 Paty
  5. David Solit
    431 Solit
  6. Zhaoshi Zeng
    82 Zeng
  7. Jinru Shia
    450 Shia
  8. Martin R Weiser
    338 Weiser
  9. Agnes Viale
    205 Viale
  10. Efsevia Vakiani
    162 Vakiani
  11. Rileen Sinha
    19 Sinha
  12. Nancy Kemeny
    346 Kemeny