Analysis of a 69-kb Contiguous Genomic Sequence at a Putative Tumor Suppressor Gene Locus on Human Chromosome 6q27

Abstract

Multiple neoplasias including B-cell non-Hodgkin's lymphoma, breast carcinoma, and ovarian carcinoma, have been associated with frequent deletions of the distal region on the long arm of human chromosome 6, suggesting the presence of one or more tumor suppressor gene(s) at this locus. Loss of heterozygosity analysis of breast and ovarian tumors has further restricted the minimal region of loss within 6q27. To further characterize this genomic region for gene content including putative tumor suppressor genes as well as other elements that may contribute to tumorigenesis, a 68940-bp contiguous sequence, encompassing markers D6S193 and D6S297, was generated by random shotgun sequencing of a cosmid, P1, and PAC contig. In addition, exon trapping was performed utilizing a subset of these clones. Sixteen trapped exons, ranging in size from 44 to 399 bp, span this approximately 69-kb region. Many other putative exons have been identified computationally. Further analysis has identified 13 potential promoters and 13 putative polyadenylation sites in the region. Northern analysis identified a transcript mapping within this interval that is expressed in ovarian, breast, and lymphoid-derived tumor cell lines. Consideration of these data, together with the demonstration of several regions of high CpG content, suggests the possibility of several genes at this locus.

Methylation of DACT2 Promotes Papillary Thyroid Cancer Metastasis by Activating Wnt Signaling

“…Human chromosome 14q22.3–32.1 is deleted in astrocytoma [40]. Human chromosome 6q27 is a region of frequent loss of heterozygosity in human cancers [41]–[47]. Based on Evolutionary and functional conservation of Wnt signaling molecules as well as human chromosomal localization, DACT1 and DACT2 genes were predicted to be potent cancer-associated genes.…”

Epigenetic regulation of the Wnt signaling inhibitorDACT2in human hepatocellular carcinoma

“…5,30 DACT2 is located on human chromosome 6q27, a region frequently associated with loss of heterozygosity in human cancers. 18,[21][22][23][24][25][26][27] region. The mixed methylation pattern of CpGs observed with BSSQ in the SNU182 cell line may represent both methylated and unmethylated alleles or both methylated and unmethylated clonal subpopulations within cultured cells.…”

UTRN on chromosome 6q24 is mutated in multiple tumors

“…Chromosome 6q deletion is usually part of the complicated karyotypic abnormalities in these tumors; however, it has been reported as a solitary change (Offit et al, 1994). Detailed mapping of the 6q deletion performed in several types of tumors indicated at least four common deleted regions at 6q14, 6q21, 6q24 and 6q27 (Qu et al, 1998;Abe et al, 1999;Hu et al, 2001;Jensen et al, 2003).…”