title: TMED6-COG8 is a novel molecular marker of TFE3 translocation renal cell carcinoma.
abstract: TFE3 translocation renal cell carcinoma is a highly aggressive malignancy which often occurs primarily in children and young adults. The pathognomonic molecular lesion in this subtype is a translocation event involving the TFE3 transcription factor at chromosome Xp11.2. Hence, the pathological diagnosis of an Xp11.2 translocation RCC is based upon morphology, TFE3 immunohistochemistry, or genetic analyses. However, due to the false-positive immunoreactivity for TFE3 IHC and expensive for TFE3 break-apart FISH assay, additional molecular markers are necessary to help provide early diagnose and individualization treatment. Owing to recent advances in microarray and RNA-Seq, Pflueger et al. have discovered that TMED6-COG8 is dramatically increased in TFE3 translocation RCCs, compared with clear cell RCCs and papillary RCCs, implying that TMED6-COG8 might be a new molecular tumor marker of TFE3 translocation RCCs. To extend this observation, we firstly validated the TMED6-COG8 expression level by qRT-PCR in RCCs including Xp11.2 translocation RCCs (n=5), clear cell RCCs (n=7) and papillary RCCs (n=5). Then, we also examined the expression level of TMED6-COG8 chimera in Xp11.2 translocation alveolar soft part sarcoma. We found that TMED6-COG8 chimera expression level was higher in Xp11.2 translocation RCCs than in ASPS (P<0.05). What's more, the expression levels of TMED6-COG8 chimera in esophagus cancers (n=32), gastric cancers (n=11), colorectal cancers (n=12), hepatocellular carcinomas (n=10) and non-small-cell lung cancers (n=12) were assessed. Unexpectedly, TMED6-COG8 chimera was decreased in these five human types. Therefore, our observations from this study indicated that TMED6-COG8 chimera might act as a novel diagnostic marker in Xp11.2 translocation RCCs.
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Yongcan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Rao
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Qunli
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Henghui
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine Nanjing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhou
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D041321:Chromosomes, Human, X; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D033921:Vesicular Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; C522290:COG8 protein, human; C069203:TFE3 protein, human; C572219:TMED6 protein, mouse; D033921:Vesicular Transport Proteins
keywords: Renal cell carcinomas; TFE3 translocation renal cell carcinomas; TMED6-COG8 chimera; diagnostic marker