Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer

Abstract

Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA-SSR1 is a dinucleotide CA repeat of the EGFR gene that can modulate EGFR transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for EGFR CA-SSR1 polymorphism and MSI status. Additionally, EGFR mRNA and protein expression levels in the tumour centre and in the invasive tumour front, compared with those in adjacent normal tissue samples, were evaluated in 80 tumour samples. An inverse association was identified between EGFR mRNA levels and the sum of repeats in both alleles of the CA-SSR1 polymorphism in normal tissues. Changes in CA-SSR1 were detected in the tumour centre as well as in the invasive tumour front and metastases in all MSI high (MSI-H) tumours. Analysis of EGFR expression at the mRNA and protein levels according to MSI status revealed lower EGFR mRNA and protein expression in MSI-H tumours than microsatellite-stable (MSS) tumours. Furthermore, higher EGFR levels in the invasive tumour front compared with in the tumour centre in MSS tumours were identified, suggesting a role of EGFR in tumour progression and higher invasive potential of MSS than MSI-H tumours.

Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population

“…The rs763317 G>A polymorphism is located in intron 1, 6.9 kilobases downstream of the polymorphism region of the dinucleotide CA repeat (near the second enhancer) in the EGFR gene [35]. Analyses of the Mitogen-Activated Protein Kinase/Extracellular-signal-Regulated Kinase (MAPK/ ERK) signaling system [36] demonstrated that the MAPK/ ERK pathway was the center of frequently altered genes throughout the progression of multiple primary lung cancers, including mutated downstream genes and altered upstream activators.…”

Genetic polymorphisms associated with the response of head and neck carcinoma to cetuximab

“…Se considera que un alelo es corto cuando las repeticiones CA son menores o iguales a 16 y un alelo es largo cuando son mayores a 17 repeticiones CA. La longitud de los alelos de este polimorfismo se correlacionan inversamente con la actividad transcripcional del gen EGFR (45,46,47). Graciano et al, 2008 (48) evaluaron el polimorfismo CA-SSR-1 conjuntamente con el SNP 61 A>G del EGF en una cohorte de 110 pacientes con CCRm cuyo estado de la mutación de KRAS era desconocido, tratados con irinotecán más cetuximab y encontraron que los pacientes con dos alelos con menos de 17 repeticiones y un genotipo 61GG presentaron una mayor SLP y SG, en cambio, Loupakis et al, 2014 (49) estudiaron 115 pacientes con CCRm y no hallaron diferencias significativas tanto en la SLP (p= 0,991) como en la SG (p = 0,261) en los portadores de alelos cortos o largos.…”