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Genome wide methylation of RASSFs associated genes in Kidney Cancer
Author(s) -
ALOKAIL MAJED S,
ALENAD AMAL M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.581.1
Subject(s) - chromophobe cell , methylation , cancer research , dna methylation , biology , oncocytoma , clear cell , clear cell renal cell carcinoma , cancer , kidney cancer , gene , renal cell carcinoma , kidney , carcinoma , genetics , oncology , medicine , gene expression
The RASSF are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers including kidney cancer. RASSF proteins have several functional domains that modulate associations with other proteins like Salvador‐RASSF‐Hippo (SARAH). RASSFs can associate via the SARAH domain with downstream kinases such as MST1 and MST2 and SAV1 in order to promote apoptosis. This study identifying differential methylation patterns that can distinguish between conventional clear cell renal cell carcinoma (ccRCC), chromophobe, oncocytoma and papillary RCC. Genome wide methylation using the Illumina Infinium Human Methylation 450 Bead Chip, RASSF 1A was highly methylated in ccRCC, Papillary and Oncocytoma tested (95%, 100% and 45% respectively), while in chromophobe, methylation was lower at only 15% of samples. Analysis of the Hippo pathway genes indicates that methylation of this pathway may vary between the cancer types in particualar methylation of MST1, which was identified to be methylated in 80% ccRCC, 38.9% papillary RCC, 20% chromophobe and 13.3% oncocytomas. Methylation of the RASSF 2 promoter was detected in 36.8% papillary RCC, 31.6% ccRCC, 16.7% chromophobe and 5.3% oncocytomas. In conclusion, the methylation levels varied across the promoters of Salvador‐RASSF‐Hippo genes associated with kidney cancer. Support or Funding Information King Saud University