EGFR and Esophageal cancer. Underpinnings, if any to the AA population.
Studies if any on the whole-exome sequencing of tumor samples from ESCC patients and reports if any on EGFR mutations in such samples. Any reference to domain-specific mutations in such cases gleaned either through whole-exome sequencing OR other studies
Results
Sample T15 harbored EGFRvIII mutation and amplification of chr7:55087058-chr7:55223523 (Figure 3a) on which the EGFR gene is located. Sample T5 was found to carry the EGFR vIVa mutation and amplification of chr7:55268106-chr7:55272949 (Figure 3b) which carries the EGFR gene.
Two tumor samples, T15 and T5, carried EGFR mutations and amplification. Sample T15 harbored EGFRvIII mutation caused by a deletion of exons 2–7, in addition to an amplification of the region, chr7:55087058-chr7:55223523 on which EGFR gene is located (Fig. 4a). Sample T5 was found to carry EGFR vIVa which represents deletion of exons 25–27, and amplification in chr7:55268106-chr7:55272949, which includes EGFR (Fig. 4b). In samples T5 and T15, we observed a mutual exclusive amplification pattern between EGFR and KRAS genes. However, amplification of cell cycle-related genes and MYC co-occurred with EGFR and with KRAS amplification.
One of the major highlights of the current study is the identification of two EGFR mutations, EGFRvIII and EGFRvIV, accompanied by amplification of EGFR, in samples T5 and T15. While amplification of wild-type EGFR has been previously reported in 7% of ESCC samples 40, EGFR mutations have not been reported before in ESCC, to the best of our knowledge. The EGFRvIII and EGFRvIV mutations, concurrent with EGFR amplifications are characteristic of Glioblastoma multiforme (GBM) 42. EGFRvIII arises from the deletion of exons 2 – 7 which code for the extracellular domain (ECD) of the EGFR protein. Loss of the EwCD renders the receptor incapable of binding to its ligand, generating constitutive signaling, tumor growth, and progression 25.