G2Cdb::Human Disease report

Disease id
D00000015
Name
Oesophageal squamous cell carcinoma
Nervous system disease
no

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001624 PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
Y (16380997) Unknown (?) Y
G00002207 CTTN
cortactin
Y (17178864) Copy Number Polymorphism (CNP) Y

References

  • Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance.

    Luo ML, Shen XM, Zhang Y, Wei F, Xu X, Cai Y, Zhang X, Sun YT, Zhan QM, Wu M and Wang MR

    State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

    Gain of chromosome 11q13 is a common event in esophageal squamous cell carcinoma (ESCC). The cortactin gene (CTTN, also EMS1), located at 11q13, plays a pivotal role in coupling membrane dynamics to cortical actin assembly. This gene has been implicated in the motility of several types of cells. In the present study, we found that the amplification and overexpression of the CTTN gene was associated with lymph node metastasis in ESCC. Functional analysis by small interfering RNA-mediated silencing of CTTN revealed that in addition to the effect on cell migration, CTTN influenced cell invasiveness by anoikis resistance. In vivo assay showed that inhibition of CTTN expression also decreased tumor growth and lung metastasis of ESCC cells. At the molecular level, we showed for the first time that the protective role of CTTN in anoikis resistance was correlated with the activation of the phosphatidylinositol 3-kinase/Akt pathway. Overall, the data suggest that CTTN is an oncogene in the 11q13 amplicon and exerts functions on tumor metastasis in ESCC.

    Cancer research 2006;66;24;11690-9

  • Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus.

    Phillips WA, Russell SE, Ciavarella ML, Choong DY, Montgomery KG, Smith K, Pearson RB, Thomas RJ and Campbell IG

    Surgical Oncology Laboratory, Peter MacCallum Cancer Centre, and Department of Surgery (St. Vincent's Hospital), University of Melbourne, Parkville, VIC, Australia. wayne.phillips@petermac.org

    Mutation of PIK3CA, the gene coding for the p110alpha catalytic subunit of phosphoinositide 3-kinase (PI3K), has been reported in a limited range of human tumors. We now report that PIK3CA is also mutated in esophageal tumors. Single-strand conformational polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) were used to screen all 20 exons of PIK3CA in 101 samples from 95 individuals with esophageal cancer and/or Barrett's esophagus. Somatic mutation of PIK3CA was detected in 4 of 35 (11.8%) of esophageal squamous cell carcinomas (SCC) and 3 of 50 (6%) adenocarcinomas. No mutations were detected in any of 17 samples of Barrett's esophagus. For PIK3CB, we screened exons 11 and 22, which code for the regions corresponding to the exon 9 and 20 mutational 'hotspots' of PIK3CA. No somatic changes were detected in PIK3CB This study extends previous observations in other tumor types by demonstrating the presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers.

    International journal of cancer 2006;118;10;2644-6

Literature (2)

Pubmed - other

  • Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance.

    Luo ML, Shen XM, Zhang Y, Wei F, Xu X, Cai Y, Zhang X, Sun YT, Zhan QM, Wu M and Wang MR

    State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

    Gain of chromosome 11q13 is a common event in esophageal squamous cell carcinoma (ESCC). The cortactin gene (CTTN, also EMS1), located at 11q13, plays a pivotal role in coupling membrane dynamics to cortical actin assembly. This gene has been implicated in the motility of several types of cells. In the present study, we found that the amplification and overexpression of the CTTN gene was associated with lymph node metastasis in ESCC. Functional analysis by small interfering RNA-mediated silencing of CTTN revealed that in addition to the effect on cell migration, CTTN influenced cell invasiveness by anoikis resistance. In vivo assay showed that inhibition of CTTN expression also decreased tumor growth and lung metastasis of ESCC cells. At the molecular level, we showed for the first time that the protective role of CTTN in anoikis resistance was correlated with the activation of the phosphatidylinositol 3-kinase/Akt pathway. Overall, the data suggest that CTTN is an oncogene in the 11q13 amplicon and exerts functions on tumor metastasis in ESCC.

    Cancer research 2006;66;24;11690-9

  • Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus.

    Phillips WA, Russell SE, Ciavarella ML, Choong DY, Montgomery KG, Smith K, Pearson RB, Thomas RJ and Campbell IG

    Surgical Oncology Laboratory, Peter MacCallum Cancer Centre, and Department of Surgery (St. Vincent's Hospital), University of Melbourne, Parkville, VIC, Australia. wayne.phillips@petermac.org

    Mutation of PIK3CA, the gene coding for the p110alpha catalytic subunit of phosphoinositide 3-kinase (PI3K), has been reported in a limited range of human tumors. We now report that PIK3CA is also mutated in esophageal tumors. Single-strand conformational polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) were used to screen all 20 exons of PIK3CA in 101 samples from 95 individuals with esophageal cancer and/or Barrett's esophagus. Somatic mutation of PIK3CA was detected in 4 of 35 (11.8%) of esophageal squamous cell carcinomas (SCC) and 3 of 50 (6%) adenocarcinomas. No mutations were detected in any of 17 samples of Barrett's esophagus. For PIK3CB, we screened exons 11 and 22, which code for the regions corresponding to the exon 9 and 20 mutational 'hotspots' of PIK3CA. No somatic changes were detected in PIK3CB This study extends previous observations in other tumor types by demonstrating the presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers.

    International journal of cancer 2006;118;10;2644-6

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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