Alternative titles; symbols
HGNC Approved Gene Symbol: CDH13
Cytogenetic location: 16q23.3 Genomic coordinates (GRCh38): 16:82,626,969-83,800,640 (from NCBI)
Lee (1996) used subtractive hybridization to identify candidate genes whose expression is altered in human breast cancer cells. One clone recovered using this approach (NB39) encodes a member of the cadherin family, CDH13. The authors determined that the CDH13 gene is expressed in normal cells but not in the majority of human tumor cells of epithelial origin, they called the CDH13 gene, H-cadherin, because its highest expression was observed in the heart. Two major mRNA transcripts were found, one of 3.7 kb and another of 4.1 kb. The open reading frame encodes a 713-amino acid polypeptide with a predicted molecular mass of 80 kD. Lee (1996) reported that the overall similarity of H-cadherin to other cadherins is 20 to 30% except for T-cadherin, where the homology is 75%. H-cadherin has common cadherin domains but lacks the cadherin cytoplasmic region.
Jee et al. (2010) noted that the CDH13 gene contains 14 exons spanning 1.2 Mb.
Lee (1996) localized the CDH13 gene to chromosome 16q24 by fluorescence in situ hybridization. Kremmidiotis et al. (1998) mapped the CDH13 gene to chromosome 16q24.2-q24.3 using somatic cell hybrid panels.
Loss of heterozygosity (LOH) for the chromosome 16p24-qter region in breast cancer had been reported by Tsuda and Hirohashi (1995). Additionally, LOH of this region was reported in prostate cancer (Carter et al., 1990) and in hepatocellular cancer (Tsuda et al., 1992). To examine the effect of H-cadherin expression on the malignant phenotype, Lee (1996) introduced H-cadherin cDNA into 2 breast tumor cell lines in which there was no basal H-cadherin expression. The transfection of H-cadherin resulted in diminished tumor cell growth and a significant change from invasive morphology to a normal cell-like morphology in an outgrowth assay. Lee (1996) concluded that downregulation of H-cadherin may be frequent in breast malignant progression and suggested that H-cadherin expression may have prognostic value as a marker for breast cancer development.
By the RT-PCR technique, Sato et al. (1998) demonstrated loss of expression of the CDH13 gene in 4 of 7 lung cancer cell lines. Three of the 4 cell lines that lost expression showed a deletion of the CDH13 locus accompanied by hypermethylation of the remaining allele. Moreover, hypermethylation was observed in 9 (45%) of 20 primary lung cancers.
Hug et al. (2004) identified T-cadherin as a receptor for the hexameric and high molecular weight species of adiponectin (605441) but not for the trimeric or globular species. Only eukaryotically expressed adiponectin bound to T-cadherin, implying that posttranslational modifications of adiponectin are critical for binding. T-cadherin is expressed in endothelial and smooth muscle cells, where it is positioned to interact with adiponectin. Because T-cadherin is a glycosylphosphatidylinositol-anchored extracellular protein, it may act as a coreceptor for a signaling receptor through which adiponectin transmits metabolic signals.
In a study of patients with stage I nonsmall cell lung cancer (NSCLC; see 211980) who underwent curative resection but had a recurrence compared to matched patients who did not have a recurrence, Brock et al. (2008) found that promoter methylation of the CDKN2A (600160), CDH13, RASSF1A (605082), and APC (611731) genes in tumors and in histologically tumor-negative lymph nodes was independently associated with tumor recurrence. Methylation of the promoter regions of CDKN2A and CDH13 in both tumor and mediastinal lymph nodes was associated with an odds ratio of recurrent cancer of 15.50 in the original cohort and an OR of 25.25 when the original cohort was combined with an independent validation cohort of 20 patients with stage I NSCLC.
For discussion of a possible association between variation in the CDH13 gene and stature as a quantitative trait, see STQTL22 (613547).
For discussion of a possible association between variation in the CDH13 gene and serum levels of adiponectin quantitative trait, see ADIPQTL5 (613836).
Brock, M. V., Hooker, C. M., Ota-Machida, E., Han, Y., Guo, M., Ames, S., Glockner, S., Piantadosi, S., Gabrielson, E., Pridham, G., Pelosky, K., Belinsky, S. A., Yang, S. C., Baylin, S. B., Herman, J. G. DNA methylation markers and early recurrence in stage I lung cancer. New Eng. J. Med. 358: 1118-1128, 2008. [PubMed: 18337602] [Full Text: https://doi.org/10.1056/NEJMoa0706550]
Carter, B. S., Ewing, C. M., Ward, W. S., Treiger, B. F., Aalders, T. W., Schalken, J. A., Epstein, J. I., Isaacs, W. B. Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc. Nat. Acad. Sci. 87: 8751-8755, 1990. [PubMed: 1978938] [Full Text: https://doi.org/10.1073/pnas.87.22.8751]
Hug, C., Wang, J., Ahmad, N. S., Bogan, J. S., Tsao, T.-S., Lodish, H. F. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc. Nat. Acad. Sci. 101: 10308-10313, 2004. [PubMed: 15210937] [Full Text: https://doi.org/10.1073/pnas.0403382101]
Jee, S. H., Sull, J. W., Lee, J.-E., Shin, C., Park, J., Kimm, H., Cho, E.-Y., Shin, E.-S., Yun, J. E., Park, J. W., Kim, S. Y., Lee, S. J., Jee, E. J., Baik, I., Kao, L., Yoon, S. K., Jang, Y., Beaty, T. H. Adiponectin concentrations: a genome-wide association study. Am. J. Hum. Genet. 87: 545-552, 2010. [PubMed: 20887962] [Full Text: https://doi.org/10.1016/j.ajhg.2010.09.004]
Kremmidiotis, G., Baker, E., Crawford, J., Eyre, H. J., Nahmias, J., Callen, D. F. Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity. Genomics 49: 467-471, 1998. [PubMed: 9615235] [Full Text: https://doi.org/10.1006/geno.1998.5281]
Lee, S. W. H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nature Med. 2: 776-782, 1996. [PubMed: 8673923] [Full Text: https://doi.org/10.1038/nm0796-776]
Sato, M., Mori, Y., Sakurada, A., Fujimura, S., Horii, A. The H-cadherin (CDH13) gene is inactivated in human lung cancer. Hum. Genet. 103: 96-101, 1998. Note: Erratum: Hum. Genet. 103: 532 only, 1998. [PubMed: 9737784] [Full Text: https://doi.org/10.1007/s004390050790]
Tsuda, H., Hirohashi, S. Identification of multiple breast cancers of multicentric origin by histological observations and distribution of allele loss on chromosome 16q. Cancer Res. 55: 3395-3398, 1995. [PubMed: 7614478]
Tsuda, H., Oda, T., Sakamoto, M., Hirohashi, S. Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin. Cancer Res. 52: 1504-1509, 1992. [PubMed: 1347253]