Disease relevance of WNT7A

• Altered HOX and WNT7A expression in human lung cancer [1].
• WNT7A was highly expressed in SW480 (colorectal cancer), BxPC-3 and Hs766T (pancreatic cancer), and was also expressed in MKN7 and MKN45 (gastric cancer) [2].
• RESULT(S): Expression of WNT7A and PAX8 was found in the normal peritoneum in approximately half of the patients with endometriosis in contrast to the controls [3].
• Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome [4].

High impact information on WNT7A

• In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs [4].
• The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout) [4].
• Yeast artificial chromosome-fluorescence in situ hybridisation (YAC-FISH) mapped the WNT7A gene to chromosome 3p25 [5].
• CpG methylation of the WNT7A gene was not detected and the WNT7A and HDAC11 proteins were normally expressed [6].
• Inactivation of WNT7A expression by aberrant CpG island methylation and WNT7A protein expression were evaluated by methylation-specific polymerase chain reaction (PCR) and immunohistochemistry, respectively [6].

Biological context of WNT7A

• Mutational analyses of WNT7A and HDAC11 as candidate tumour suppressor genes in sporadic malignant pancreatic endocrine tumours [6].
• These tumours were examined for inactivating mutations of WNT7A and HDAC11 by direct sequencing of all exons and intron-exon boundaries [6].
• Results No point mutations, deletion or insertions were detected in either WNT7A or HDAC11 in any of the PETs [6].

Anatomical context of WNT7A

• WNT7A was highly expressed in fetal lung, adult testis, lymph node, and peripheral blood leukocytes [2].
• WNT7A was relatively highly expressed in temporal lobe, occipital lobe, parietal lobe, paracentral gyrus of cerebral cortex, caudate nucleus, hippocampus, medulla oblongata and putamen within adult brain [2].
• WNT7A mutations in patients with Müllerian duct abnormalities [7].
• During dorsal-ventral (DV) patterning of the vertebrate limb, WNT7A is expressed in dorsal limb ectoderm and activates the expression of LMX1 (in chick; Lmx1b in mouse) in dorsal limb mesenchyme, resulting in the appropriate development of dorsal cell fates [8].
• Interferon-c acts on the endometrial lumenal epithelium to induce WNT7A and to stimulate LGALS 15, cathepsin L and cystatin C, which are candidate regulators of conceptus development and implantation [9].

Associations of WNT7A with chemical compounds

• WNT7B, but not WNT7A, was slightly up-regulated by all-trans retinoic acid in NT2 cells [2].

Other interactions of WNT7A

• Phylogenetic analyses on WNT family members revealed that WNT16 was most closely related to WNT7A and WNT7B paralogs [10].

Analytical, diagnostic and therapeutic context of WNT7A

• In patients with endometriosis WNT7A and PAX8 in histologically normal peritoneum (with no evidence of endometriosis, endosalpingiosis, or other changes) were confirmed by in situ hybridization [3].
• Furthermore, we have isolated a genomic clone of WNT7A and mapped it to chromosome 3p25 by fluorescent in situ hybridization [11].

References