Single‐nucleotide polymorphism‐mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma

Qin, Yan; Fu, Li; Sham, Pak C.; Kwong, Dora Lai Wan; Zhu, C. Y.; Chu, Kevin K.W.; Li, Yan; Guan, Xin Yuan

doi:10.1002/ijc.23577

Cited by 51 publications

(52 citation statements)

References 22 publications

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“…CHL1 is a member of the family of L1 neural cell adhesion molecules and has been reported to have regulatory functions that are pivotal to nervous system development (41). Additionally, a low-level transcript of CHL1 associated with loss of 3p26.3 has been reported in esophageal squamous cell carcinoma (42). These observations in combination with our results suggest that CHL1 is a candidate tumor suppressor gene associated with aggressiveness of OSCC.…”

Section: Discussionsupporting

confidence: 83%

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

et al. 2011

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Abstract. Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide and the prognosis for patients with advanced-stage OSCC is particularly poor. To identify DNA copy number aberrations and candidate genes associated with a poor or favorable outcome, we analyzed the genome profiles of OSCC tumors by array-based comparative genomic hybridization (A-CGH). This technique uses DNA microarray technology to detect genomic copy number variations at a higher resolution level than chromosome-based CGH. Fifty patients with primary OSCCs were included in the study. Of these 50 patients, 37 were treated surgically and 13 were treated without surgery and had received irradiation and/or chemotherapy. All samples were analyzed by A-CGH. Gains were detected frequently (>50%) at chromosomal regions 5p15. 33, 7p22.3, 8q21.1-24.3, 9q34.3, 11q13, 16p13.3 and 20q13.3. Losses were frequently detected at 3p22, 3p14 and 4q35.2. High-level gains were recurrently (>10%) detected at each of 5p15, 7p22, 7p11, 8q24, 11q13, 11q22 and 22q11. Gains of 2p25.1, 11p15, 16p13.3, 16q24.3 and 20q13.3 were inversely correlated with nodal metastasis. In 37 of the 50 OSCC patients treated with surgery, gains of 8q12.1-24.22 and losses of 3p26.2-3 were associated with disease-specific survival (p<0.01). Loss of a 0.2 Mb chromosomal region in 3p26.3 was associated with a poor prognostic outcome in the Kaplan-Meier analysis (p<0.01 by the log-rank test). Multivariate analysis revealed that loss of 3p26.3 is an independent prognostic factor (p<0.01) of OSCC. Loss of a 0.2 Mb chromosomal region in 3p26.3 including the CHL1 (cell adhesion molecule with homology to L1CAM1) gene was identified as a novel potential marker for predicting the prognosis of patients with OSCC.

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Section: Discussionsupporting

confidence: 83%

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

et al. 2011

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“…The genetic abnormalities of these genes at 3p have an important role in the development of lung cancer and renal cancer. In our recent study, we provided the first evidence that 3p24 was one of the most frequently deleted regions in ESCC and PCAF was identified as a candidate TSG (Qin et al, 2008). In this study, we found that mRNA expression of PCAF was absent in 44.4% of ESCC cell lines and 57.5% of primary ESCC tumors.…”

Section: Discussionmentioning

confidence: 54%

“…When KYSE510 cells were treated with 5-aza-dC, the expression of PCAF could be reactivated (Figure 2d), indicating that both promoter methylation and DNA copy loss contributed to the absent expression of PCAF gene. In our previous study, the loss of one PCAF allele has been detected in 14/40 (35%) of ESCC specimens by single-nucleotide polymorphism array (Qin et al, 2008). In these cases, the downregulation of PCAF was detected in 23 (57.5%) of the specimens.…”

Section: Downregulation Of Pcaf Is Frequently Detected In Esccsmentioning

confidence: 79%

“…In our recent study, the single-nucleotide polymorphism-mass array approach was applied to investigate LOH at 3pter-p14.1 in 100 primary ESCC cases with 350 single-nucleotide polymorphism markers. Four commonly deleted regions at 3p, including 3p24, were detected (Qin et al, 2008). One candidate TSG, p300/CBP-associated factor (PCAF), at 3p24 was further characterized in this study.…”

Section: Introductionmentioning

confidence: 89%

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Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma

et al. 2009

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Deletion of 3p is one of the most frequent genetic alterations in many tumors, including esophageal squamous cell carcinoma (ESCC). In our recent study, deletion of 3p24 was frequently detected in ESCC and one candidate tumor suppressor gene (TSG), p300/CBP-associated factor (PCAF), was identified within the region. In this study, downregulation of PCAF was detected in 23/40 (57.5%) of primary ESCCs and 4/9 (44.4%) of the ESCC cell lines. A further study found that downregulation of PCAF was also associated with hypermethylation of the promoter region of PCAF gene. Methylation-specific PCR found that promoter methylation was detected in 28/40 (70%) of primary ESCCs and 5/9 (55.6%) of ESCC cell lines. In addition, the expression of PCAF could be reactivated in ESCC cell line KYSE510 after demethylation treatment with 5-azadC. Functional studies showed that PCAF was able to suppress tumorigenicity of ESCC cells both in vitro and in vivo, including foci formation, colony formation in soft agar and tumor formation in nude mice. Molecular study found that the tumor suppressive mechanism of PCAF was associated with its role in cell cycle arrest at the G1/S checkpoint by the downregulation of CDK2 and upregulation of p21 waf1/Cip1 , Smad4, Rb and p27 Kip1 . In conclusion, PCAF might be the target TSG responsible for the 3p24 deletion event, which has an important role in the development and progression of ESCC.

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“…In acute myeloid leukemia (AML), patients with high expression of miR-191 have significantly worse overall and event-free survival than AML patients with low expression (20). Furthermore, PLCD1 and RNF139, two predicted candidate target genes of miR-191, are tumor suppressors in esophageal squamous cell carcinoma and human hereditary kidney cancer, respectively (21,22). miR-93 is up-regulated in gastric cancer tissues compared to the corresponding normal tissues (23).…”

Section: Discussionmentioning

confidence: 99%

5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro

Bai¹

2009

Oncol Rep

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Abstract. MicroRNAs (miRNAs) have recently taken center stage in the field of human molecular oncology. Most of the chemotherapeutics are able to interfere with nucleic acid metabolism and gene expression. The purpose of this study was to determine how 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) modify the expression profiles of miRNAs in HCT-8 and HCT-116 colon cancer cells and whether the pharmacodynamic mechanisms of the chemotherapeutics could rely in part on their influence on miRNA expression. The expression profiles of miRNAs were determined using a miRNA microarray containing 856 human miRNA probes. The expression of selected miRNAs was then validated by real-time RT-PCR. Fifty-six up-and 50 down-regulations of miRNA expression with statistical significance were identified in colon cancer cells following exposure to 5-FU or L-OHP compared to matched control cells. The down-regulations of miR-197, miR-191, miR-92a, miR-93, miR-222 and miR-1826, whose expression was significantly down-regulated in both cell lines after the treatment of one drug or in one cell line following exposure to either drug, were further validated. Analysis of the relevant literature indicated that, in line with the tumor suppressive activity of 5-FU and L-OHP, the six down-regulated miRNAs might function as oncogenes due to their overexpression in cancers, and some of them correlated with the poor prognosis and treatment-resistance of cancer. In conclusion, we identify the modification of miRNA expression profiles in colon cancer cells following exposure to 5-FU and L-OHP, and our results indicate that their pharmacodynamic mechanisms could rely in part on their influence on the down-regulated miRNA expression.Further studies are needed to determine whether these miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference.

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Single‐nucleotide polymorphism‐mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma

Cited by 51 publications

References 22 publications

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma

5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro

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