BAC Clones Related to Prognosis in Patients with Esophageal Squamous Carcinoma: An Array Comparative Genomic Hybridization Study

Hirasaki, Shigeo; Noguchi, Tsuyoshi; Mimori, Koshi; Onuki, Junko; Morita, Keiko; Inoue, Hiroshi; Sugihara, Kenichi; Mori, Masaki; Hirano, Takashi

doi:10.1634/theoncologist.12-4-406

Cited by 25 publications

(20 citation statements)

References 37 publications

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“…In gastric cancer and breast cancer, FBXW7 expression is suppressed by p53 mutation (14,15). In this study, genomic alteration as FBXW7 regulatory mechanism in ESCC was investigated because a copy number loss had been detected at chromosome 4q in approximately 30-40% of ESCC samples in previous studies (26)(27)(28). FBXW7 mRNA expression in ESCC was significantly associated with FBXW7 copy number.…”

Section: Discussionmentioning

confidence: 98%

Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

et al. 2012

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Abstract. FBXW7 is a tumor suppressor gene that plays a role in cell cycle regulation via Myc degradation. However, the clinical significance of FBXW7 in esophageal squamous cell carcinoma (ESCC) has not been evaluated. The purpose of this study was to assess the clinical significance of FBXW7 for prognosis in human ESCC. Real-time RT-PCR was used to examine the expression of FBXW7 to determine its clinicopathological significance in 75 cases of ESCC. Overall survival rate was calculated using the Kaplan-Meier method, while multivariate survival was analyzed with the Cox hazard model. FBXW7 suppression analysis was performed to examine proliferation potency and Myc expression in the FBXW7 siRNA groups. The relationship between FBXW7 expression and the copy number loss of FBXW7 was examined in clinical samples of ESCC. Finally, FBXW7 copy number loss was linked to prognosis in 42 ESCC patients. FBXW7 expression in cancer was lower compared to non-cancer tissues (P=0.003) and is an independent prognostic factor. The proliferation rates and Myc protein expression were significantly enhanced in FBXW7 siRNA cells compared to the controls. Cases with a loss of FBXW7 copy number had low FBXW7 expression and a poorer prognosis than cases with no loss of copy number. Genetic alterations in esophageal cancer lead to the loss of FBXW7 expression and increased cell proliferation. These genetic alterations of FBXW7 status may provide a prognostic factor for ESCC patients. IntroductionEsophageal squamous cell carcinoma (ESCC) accounts for most esophageal cancers in East Asia. Although the sensitivity of ESCC to chemoradiotherapy is relatively high, patients with progressive ESCC have poorer prognoses (1, 2). Tumor suppressor inactivation (e.g. p53, p16, RB) and oncogene activation (e.g. Myc, and cyclin D) are involved in ESCC progression (3). In particular, the Myc transcription factor and its downstream targets (e.g., Cyclin D and CDKs) are associated with carcinogenesis and progression of many cancers, including ESCC. The finding that suppression of Myc greatly inhibits tumor formation, has made Myc a promising therapeutic target (4).FBXW7 is an F-box protein that forms one of the four subunits of SCF ubiquitin ligase complexes, which induce the degradation of positive cell cycle regulators (oncoproteins) such as Myc (5-7). The degradation of Myc by FBXW7 leads to cell cycle exit (G0 phase); therefore, altered FBXW7 expression is considered a major cause of carcinogenesis or carcinoma development (8-10). Clinically, low expression of FBXW7 in human solid tumors such as glioma, colorectal cancer and gastric cancer produces a poor prognosis (11)(12)(13)(14). FBXW7 mutation, transcriptional control by p53 and copy number loss are the primary mechanisms of FBXW7 inactivation (10,13-15), which is consistent with our finding that the low expression of FBXW7 in colorectal cancer is due to copy number loss. A deletion of chromosome 4q, which includes FBXW7, has been reported in 30-40% of ESCC cases and is associated with a poor pro...

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Section: Discussionmentioning

confidence: 98%

Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

et al. 2012

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“…Absence of EML4 -ALK transcript in GI tract and breast cancers Y Fukuyoshi et al revealed chromosomal rearrangements in several kinds of cancers (Mitelman et al, 2004;Hirasaki et al, 2007). The report of the TMPRSS2 -ERG fusion in prostate cancer by Tomlins et al (2005) is probably the first description of such a gene fusion in solid cancers.…”

Section: Eml4-alk Gapdhmentioning

confidence: 96%

EML4–ALK fusion transcript is not found in gastrointestinal and breast cancers

et al. 2008

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Fusion genes have been identified as chromosomal rearrangements in certain cancers, such as leukaemia, lymphoma, and sarcoma. The EML4 -ALK (EML4: echinoderm microtubule-associated-protein-like 4; ALK: anaplastic lymphoma kinase) fusion gene has been identified as an oncogene in non-small-cell lung cancer (NSCLC). This study examined the presence of this fusion transcript in gastrointestinal and breast cancers. We evaluated the expression of the EML4 -ALK transcript in 104 lung cancer cases and in 645 gastrointestinal and breast cancer samples. Only one of the lung cancer samples tested positive for the EML4 -ALK fusion transcript, whereas none were detected in 555 gastrointestinal and 90 breast cancer cases. Our data suggest that the EML4 -ALK fusion transcript is not present in gastrointestinal or breast cancers and is specific to NSCLC.

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“…Several studies have identified that losses of 9p21.3, 16p13.3 and 18q22-qter and gains of 5p15, 7p22.1, 11q13.3 and 19p13.11 were the most frequent genomic aberrations in ESCC (3)(4)(5). Functional studies identified a number of candidate target driver genes of genomic aberration.…”

Section: Introductionmentioning

confidence: 99%

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

et al. 2016

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Abstract. The aim of the present study was to identify the candidate target genes of genomic aberrations in esophageal squamous cell carcinoma (ESCC). Array comparative genomic hybridization (CGH) and quantitative polymerase chain reaction were applied to analyze the copy number changes and expression level of candidate genes, respectively. Integrative analysis revealed that homozygous deletions of cyclin-dependent kinase inhibitor (CDKN) 2A and CDKN2B and gains of fascin actin-bundling protein 1 (FSCN1) and homer scaffolding protein 3 (HOMER3) occurred frequently in ESCC. The results demonstrated that the homozygous deletion of CDKN2A or CDKN2B was significantly associated with lymph node metastasis. Notably, the expression of CDKN2A and CDKN2B was lower in dysplasia than in normal esophageal epithelium. We also observed that the copy number increase of FSCN1 was significantly associated with pT, pN and pStage, and that the gain of HOMER3 was significantly linked with pN and pStage. We further revealed that FSCN1 and HOMER3 were overexpressed in ESCC, and that their overexpression was correlated with copy number increase. In conclusion, CDKN2A, CDKN2B, FSCN1 and HOMER3 are candidate cancer-associated genes and may play a tumorigenic role in ESCC.

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BAC Clones Related to Prognosis in Patients with Esophageal Squamous Carcinoma: An Array Comparative Genomic Hybridization Study

Cited by 25 publications

References 37 publications

Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

EML4–ALK fusion transcript is not found in gastrointestinal and breast cancers

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

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