Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing.

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Daniela S BasseresDaniel B Costa

Abstract

We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p = 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p < 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173, 55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased su...Continue Reading

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Citations

Mar 31, 2015·Oncogene·W K C Cheung, D X Nguyen
Jan 21, 2015·Developmental Biology·Vlasta LungovaSusan L Thibeault
Jul 29, 2016·Human Molecular Genetics·Rob HoutmeyersRuth M Arkell
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Aug 10, 2019·Cellular Oncology (Dordrecht)·Álvaro Quintanal-Villalonga, Sonia Molina-Pinelo

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