Disease relevance of ZMYND10

• Previously, the BLU candidate tumour suppressor gene (TSG) encoded by a gene-rich critical deleted region in 3p21.3 was found to be inactivated rarely in lung cancer, although expression was downregulated in a subset of lung tumour cell lines [1].
• Exogenous expression of BLU in neuroblastoma (SK-N-SH) and NSCLC (NCI-H1299) resulted in reduced colony formation efficiency, in vitro [1].
• In 2 corresponding specimens of hepatitis B virus-related liver cirrhosis, BLU methylation was also observed, but not in uninvolved normal liver tissue [2].
• We analyzed the methylation status of RASSF1A, BLU and SEMA3B in 35 hepatocellular carcinomas (HCCs) and 15 cholangiocarcinomas (CCs) by methylation-specific PCR and loss of heterozygosity (LOH) at 3p21.3 after microdissection [2].
• Expression of candidate chromosome 3p21.3 tumor suppressor genes and down-regulation of BLU in some esophageal squamous cell carcinomas [3].

High impact information on ZMYND10

• However, CIMP was significantly associated with methylation of promoter CGIs of the RASSF1A and BLU tumor suppressor genes [4].
• BLU is one of the candidate tumor suppressor genes (TSGs) in this region [5].
• In addition to methylation, homozygous deletion of BLU was found in 7/29 (24%) of tumors [5].
• However, in all seven NPC cell lines examined, BLU expression was downregulated and inversely correlated with promoter hypermethylation [5].
• The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma [5].

Biological context of ZMYND10

• However, no functional studies have yet verified the functional role of BLU/ZMYND10 as a tumor suppressor gene [6].
• Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma [6].
• In contrast, downregulation of BLU/ZMYND10 in these tumor suppressive clones by doxycycline treatment restored the tumor formation ability [6].
• In the current study, a gene inactivation test (GIT) utilizing a tetracycline regulation system was used to study the functional role of BLU/ZMYND10 [6].
• Furthermore, methylation of the BLU promoter region was detected in primary sporadic SCLC (14%), NSCLC (19%) and neuroblastoma (41%) [1].

Anatomical context of ZMYND10

• Biallelic epigenetic inactivation of BLU was also observed in three cell lines [5].
• BLU is highly expressed in testis and normal upper respiratory tract tissues including nasopharynx [5].

Associations of ZMYND10 with chemical compounds

• When BLU/ZMYND10 is expressed in the absence of doxycycline, the stable transfectants were able to induce tumor suppression in nude mice [6].
• Treatment of NPC cell lines with 5-aza-2'-deoxycytidine activated BLU expression along with promoter demethylation [5].
• We illustrate and discuss when the BLUE or BLUP will be a better estimate of a subject's latent value given a single measure on a subject, concluding that the BLUP estimator should be routinely used for total cholesterol and per cent kcal from fat, with a modified BLUP estimator used for large observed values of leisure time activity [7].
• The predicted genetic responses were calculated by studying the differences between the S and C lines in averaged values of five traits of the BLUP animal model [8].

Other interactions of ZMYND10

• In the NPC cell lines, loss of BLU expression correlated with hypermethylation of the CpG island promoter sequence, and expression was restored after treatment with 5'-aza-2'-deoxycytidine [9].

Analytical, diagnostic and therapeutic context of ZMYND10

• Methylation specific PCR analysis revealed that the BLU promoter was highly methylated in 74% (17 of 23) of primary tumors in which BLU was downregulated, whereas only 2 of 9 non-neoplastic nasopharyngeal epithelia exhibited hypermethylation in the BLU promoter region [9].
• Animals were evaluated with a conventional BLUP animal model or with a model using marker information [10].

References