Genomic assessments of the frequent loss of heterozygosity region on 8p21.3∼p22 in head and neck squamous cell carcinoma

Abstract

Most human cancers are characterized by genetic instabilities. Chromosomal aberrations include segments of allelic imbalance identifiable by loss of heterozygosity (LOH) at polymorphic loci, which may be used to implicate regions harboring tumor suppressor genes. Here we performed whole genome LOH profiling on over 40 human head and neck squamous cell carcinoma (HNSCC) cell lines. Several frequent LOH regions have been identified on chromosomal arms 3p, 4p, 4q, 5q, 8p, 9p, 10p, 11q, and 17p. A genomic region of ∼7 Mb located at 8p22-p21.3 exhibits the most frequent LOH (87.9%), which suggested that this region harbors important tumor suppressor gene(s). Mitochondrial tumor suppressor gene 1 (MTUS1) is a recently identified candidate tumor suppressor gene that resides in this region. Consistent down-regulation in expression was observed in HNSCC for MTUS1 as measured by real-time quantitative RT-PCR. Sequence analysis of MTUS1 gene in HNSCC revealed several important sequence variants in the exon regions of this gene. Thus, our results suggested that MTUS1 is one of the candidate tumor suppressor gene(s) reside in 8p22-p21.3 for HNSCC. The identification of these candidate genes will facilitate the understanding of tumorigenesis of HNSCC. Further studies are needed to functionally evaluate those candidate genes.

Angiotensin II type 2 receptor-interacting protein 3a suppresses proliferation, migration and invasion in tongue squamous cell carcinoma via the extracellular signal-regulated kinase-Snai2 pathway

“…MTUS1/ATIP is one of the candidate tumor suppressor genes located in the chromosomal region 8p22-p21.3, which was identified in our previous study as one of the most frequent LOH (87.9%) sites in oral cancer (2). Numerous studies have demonstrated that the deregulation of MTUS1/ATIP is associated with several types of cancer (5-11,13), including hepatocellular, bladder, breast, colon, prostate and head and neck cancer.…”

“…TSCC is characterized by genetic instabilities, including frequent loss of heterozygosity (LOH) at the chromosomal region 8p21.3-p22 (2). Microtubule-associated tumor suppressor gene (MTUS1) is one of the candidate tumor suppressor genes that reside in this chromosomal region.…”

“…Microtubule-associated tumor suppressor gene (MTUS1) is one of the candidate tumor suppressor genes that reside in this chromosomal region. In our previous study using single-nucleotide polymorphism (SNP) array-based LOH profiling on a large panel of oral cancer cell lines, a frequent LOH region was identified at 8p22-p21.3, a region containing the MTUS1 gene, which was initially identified as a potential tumor suppressor gene in pancreatic cancer (2). MTUS1 has been identified as an 8p22 candidate tumor suppressor gene encoding a family of angiotensin II type 2 (AT2) receptor-interacting proteins (ATIPs).…”

Down-regulation of MTUS1 in human colon tumors

“…Since it already has been reported that CpNpG methylation can occur in vivo and that methylation of these islands is suspected to stabilize the DNA (28), the hypomethylation of CpNpG islands could be a mechanism for the MTUS1 inactivation. Nevertheless, some published investigations have found deletion and some small mutations in the exon region of MTUS1, so that further analyses are needed to understand the mechanism of down-regulation in this gene (19,21).…”

“…Previously, the inhibitory effect of MTUS1 on cell proliferation was linked to the growth inhibitory signaling cascade by trans-inactivation of receptor tyrosine kinases in insulin, bFGF, PDGF and EGF-induced ERK2 activation (17). A previously published investigation demonstrated a significant down-regulation of MTUS1 in ovarian carcinoma tissues, implicating a possible role of MTUS1 on the development of ovarian carcinoma (18 (19)(20)(21). The gene responsible for tumor progression in colon cancer, located at chromosome 8p21.3-22 near marker D8S254, would be expected to be down-regulated in colon cancer (1,10).…”