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Menzies Health Institute Queensland menzies.griffith.edu.au School of Medicine, Griffith University, Gold Coast, Australia Md Hakimul Haque, Vinod Gopalan,

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Presentation on theme: "Menzies Health Institute Queensland menzies.griffith.edu.au School of Medicine, Griffith University, Gold Coast, Australia Md Hakimul Haque, Vinod Gopalan,"— Presentation transcript:

1 Menzies Health Institute Queensland menzies.griffith.edu.au School of Medicine, Griffith University, Gold Coast, Australia Md Hakimul Haque, Vinod Gopalan, Riajul Wahab, Farhadul Islam, Robert Anthony Smith, Alfred King-yin. Lam Cancer Molecular Pathology in Cancer Research Centre of Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia FAM134B (Family With Sequence Similarity 134, Member B) also known as JK1 is a novel protein-coding gene which is placed at 5p15.1 chromosome downstream to δ-catenin (Tang et al., 2007). Recent studies suggest that FAM134B (JK1) play a key role in regulating cancer cell biology and in autonomic neurological disorders (Tang et al., 2007, Kurth et al., 2009). Previously our group reported that FAM134B has oncogenic properties in oesophageal squamous cell carcinoma (ESCC) while in colon adenocarcinoma, it acts as tumour suppressor gene (Tang et al., 2007; Kasem et al., 2014b). However, the exact role of FAM134B in ESCC remains unclear. Current study aims to detect the copy number of FAM134B in fresh ESCC tissue samples. The results will be correlated the clinicopathological significance of FAM134B in ESCC. After histopathological analysis, 102 matched fresh tissue samples of ESCC tissues and non-cancer adjacent tissues were recruited. DNA copy numbers of FAM134B were studied by a Real-Time polymerase chain reaction (PCR) detection system.  The percentage of JK1 (FAM134B) copy number changes are implies that this gene might act as both oncogene and tumor suppressor in the progression of ESCC.  In-vitro and in-vivo analysis are needed to confirm its exact role in the pathogenesis of oesophageal squamous cell carcinoma. Identification of FAM134B (JK1) in ESCC tissues Figure 1. FAM134B (JK1) was detectable in all the samples used in the DNA study. A 106-bp fragment was observed for FAM134B and a 225-bp fragment was found for control gene, haemoglobin delta (HBD) in 2% agarose gel after performing real time PCR. FAM134B (JK1) and HBD were present in all the samples (2-14) except for the water control (15). Fifty-base pair DNA ladder was used for comparison. Figure 2. FAM134B (JK1) copy number changes in oesophageal squamous cell carcinoma. In ESCC, 37% (38/102) showed increased FAM134B copies whereas 35% (36/102) showed loss of FAM134B copies relative to matched non-tumour tissues. The DNA copy number of FAM134B in the cancer population was found to have no relationship with the age of the patients, size, grade, histological subtypes or TNM staging of the ESCCs. Tang WK, Chui CH, Fatima S, Kok SH, Pak KC, Ou TM, Hui KS, Wong MM, Wong J, Law S, Tsao SW, Lam KY, Beh PS, Srivastava G, Chan AS, Ho KP, Tang JC. Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma. Int J Mol Med. 2007;19:915-23. Kurth I, Pamminger T, Hennings JC, Soehendra D, Huebner AK, Rotthier A, Baets J, Senderek J, Topaloglu H, Farrell SA, Nürnberg G, Nürnberg P, De Jonghe P, Gal A, Kaether C, Timmerman V, Hübner CA. Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat Genet. 2009;41:1179-81 Kasem K, Gopalan V, Salajegheh A, Lu CT, Smith RA, Lam AK. The roles of JK-1 (FAM134B) expressions in colorectal cancer. Exp Cell Res. 2014 (b);326:166-73. Table 1: Clinicopathological features and JK1 (FAM134B) genetic changes FAM134B (JK1) copy number variations Introduction Aims Results Conclusion Methodology References Natural copy number variations of FAM134B (JK1) in oesophageal squamous cell carcinoma CharacteristicsNumberAmplificationDeletionNo changeP value Site Lower12 (21.1%)4 (16.0%)5 (31.3%)3 (18.8%)0.77 Middle40 (70.2%)19 (76.0%)10 (62.5%)11 (68.8%) Upper5 (8.8%)2 (8.0%)1 (6.3%)2 (12.5%) Lymph node metastasis 020 (35.1%)7 (28.0%)7 (43.8%)6 (37.5%)0.57 137 (64.9%)18 (72.0%)9 (56.3%)10 (62.5%) Distant metastasis 053 (93.0%)23 (92.0%)16 (100.0%)14 (87.5%)0.41 13 (5.3%)2 (8.0%)0 (0.0%)1 (6.3%) TNM Stage Stage I1 (1.8%)1 (4.0%)0 (0.0%) 0.68 Stage II14 (24.6%)6 (24.0%)5 (31.3%)3 (18.8%) Stage III38 (66.7%)16 (64.0%)11 (68.8%) Stage IV3 (5.3%)2 (8.0%)0 (0.0%)1 (6.3%) Survival status Alive10 (17.5%)6 (24.0%)3 (18.8%)1 (6.3%)0.49 Dead44 (77.2%)18 (72.0%)13 (81.3%) Histological Grade Well32 (56.1%)14 (56.0%)10 (62.5%)8 (50.0%)0.28 Moderate13 (22.8%)8 (32.0%)1 (6.3%)4 (25.0%) Poor12 (21.1%)3 (12.0%)5 (31.3%)4 (25.0%) Survival analysis Figure 3. The correlation between patients’ survival and FAM134B (JK1) copy number changes in oesophageal squamous cell carcinoma. Patients with FAM134B (JK1) copy number deletion had a lower survival rates compared to patients with amplification in DNA copy numbers.


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