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EGFR
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Interpretation 267
Tier 2
EGFR
Variants
EGFR R776H
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

The epidermal growth factor receptor (EGFR) is a cell surface receptor belonging to the ErbB family tyrosine kinase receptors. EGFR is involved in cell growth control through its role in the two main intracellular pathways, the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase- (PI3K-) protein kinase B (AKT) pathway. The over-expression or mutation of EGFR may be responsible for the constitutive activation of these pathways. In the colorectal cancer, the EGFR has been found to be frequently over expressed, and may be associated with tumor stage and prognosis. In a subset of such patients, the addition of anti-EGFR monoclonal antibodies to the conventional chemotherapeutic regimens may expand response rates and increase progression-free survival. Somatic EGFR mutations are infrequent in colorectal cancers. The frequency varies from 0.34 to 3.3% in Western population, and from 12% to 22.4% in Asians. R776H is a recurrent mutation in the hinge region of the kinase domain and is known to activate EGFR in a ligand independent manner. In some cases, the possibility of R776H variant being of germline origin, cannot be excluded. The clinicopathologic correlation of EGFR mutations in colorectal cancers continues to be explored.

Citations
  1. Oh BY, et al. Epidermal growth factor receptor mutations in colorectal cancer patients. J Korean Soc Coloproctol 2011;27(3):127-32
  2. Barber TD, et al. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med 2004;351(27):2883
  3. Krasinskas AM EGFR Signaling in Colorectal Carcinoma. Patholog Res Int 2011;2011():932932
  4. Metzger B, et al. The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain. BMC Med Genet 2011;12():144
  5. van Noesel J, et al. Activating germline R776H mutation in the epidermal growth factor receptor associated with lung cancer with squamous differentiation. J Clin Oncol 2013;31(10):e161-4
  6. Misale S, et al. Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution. Cancer Discov 2014;4(11):1269-80
  7. Ruan Z, et al. Mechanistic Insights into R776H Mediated Activation of Epidermal Growth Factor Receptor Kinase. Biochemistry 2015;54(27):4216-25
Last updated: 2016-05-05 13:40:13 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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