Characterization of Copy Number Variations in Oral Cavity Squamous Cell Carcinoma Reveals a Novel Role for MLLT3 in Cell Invasiveness

AbstractBackground.DNA copy number variations (CNVs) are a hallmark of cancer, and the current study aimed to demonstrate the profile of the CNVs for oral cavity squamous cell carcinoma (OSCC) and elucidate the clinicopathological associations and molecular mechanisms of a potential marker derived from CNVs, mixed‐lineage leukemia translocated to chromosome 3 protein (MLLT3), in OSCC carcinogenesis.Materials and Methods.CNVs in 37 OSCC tissue specimens were analyzed using a high‐resolution microarray, the OncoScan array. Gene expression was analyzed by real‐time polymerase chain reaction in 127 OSCC and normal tissue samples. Cell function assays included cell cycle, migration, invasion and chromatin immunoprecipitation assays.Results.We found a novel copy number amplified region, chromosome 9p, encompassing MLLT3 via the comparison of our data set with six other OSCC genome‐wide CNV data sets. MLLT3 overexpression was associated with poorer overall survival in patients with OSCC (p = .048). MLLT3 knockdown reduced cell migration and invasion. The reduced invasion ability in MLLT3‐knockdown cells was rescued with double knockdown of MLLT3 and CBP/p300‐interacting transactivator with ED rich carboxy‐terminal domain 4 (CITED4; 21.0% vs. 61.5%). Knockdown of MLLT3 impaired disruptor of telomeric silencing‐1‐like (Dot1L)‐associated hypermethylation in the promoter of the tumor suppressor, CITED4 (p
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Head and Neck Cancers Source Type: research