Molecular biomarker profile of EGFR copy number, KRAS and BRAF mutations in colorectal carcinoma

Rong Rong, Jamie Tull, Shengle Zhang


Anti-EGFR therapy is approved by US Food and Drug Administration (FDA) as mono-therapy or as part of combination chemotherapy for metastatic colorectal carcinoma. Monoclonal anti-EGFR antibodies cetuximab and panitumumab have shown benefits for those patients with wild-type KRAS gene. Patients with KRAS mutation in codon 12 or 13 are unresponsive to targeted anti-EGFR therapy. Mutations of BRAF, the main downstream target gene of KRAS, also negatively impact the patients’ response to the therapy. On the contrary, EGFR gene amplification in colon cancer predicts a better response to anti-EGFR therapy. The correlation of EGFR amplification with KRAS and BRAF mutation status is not only of academic interests but also of clinical importance. Previous studies have shown that EGFR mutation is mutually exclusive with KRAS and BRAF mutations in lung cancer. However, there is limited data on colorectal cancer so far. In this study, 28 colorectal cancer samples are tested for KRAS and BRAF mutations by PCR and for EGFR gene copy number by fluorescence in situ hybridization (FISH). EGFR high-copies, KRAS mutation and BRAF mutation are found in 15 (54%), 13 (46%) and 3 (11%) samples, respectively. A mutually-exclusive pattern is seen between KRAS mutations (13 positive samples) and BRAF mutations (3 positive samples). However, high EGFR high copy number is not "mutually-exclusive" with KRAS or BRAF mutations. Six samples with KRAS mutations and 2 with BRAF mutation show "co-existing" high EGFR copy number. These account for 29% of total cases tested. Five cases are triple negative for EGFR, KRAS and BRAF alterations. The results from our study indicate that high EGFR copy number with concurrent KRAS or BRAF mutations is quite common in colon cancer and the therapeutic response with anti-EGFR agents in this patient population requires further investigation.


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Journal of Solid Tumors

ISSN 1925-4067(Print)   ISSN 1925-4075(Online)

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