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Spotlight on Familial and Hereditary Gastric Cancer pp 87–96Cite as

Alternative Mechanisms to Germline CDH1 Mutations in Hereditary Diffuse Gastric Cancer

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Abstract

Germline mutations in the CDH1 gene remained for more than 10 years the single molecular defect in hereditary diffuse gastric cancer families screened worldwide. The remaining families which completed the International Gastric Cancer Linkage Consortium criteria kept genetically unexplained, raising great concern from a clinical management standpoint.

Some authors reasoned and proved that other genetic events at the CDH1 locus, such as large genomic deletions, germline promoter methylation or deregulation of trans-acting factors leading to near-monoallelic expression of CDH1, could be found in families with multiple cases of diffuse gastric cancer.

In this chapter, the current knowledge on CDH1 locus associated germline defects in CDH1-mutation negative families will be revised.

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Abbreviations

AI:

Allelic Imbalance

CGH:

Comparative Genomic Hybridization

HDGC:

Hereditary Diffuse Gastric Cancer

HNPCC:

Hereditary Non-Polyposis Colorectal Cancer

IGCLC:

International Gastric Cancer Linkage Consortium

MLPA:

Multiplex Ligation-dependent Probe Amplification

NAHR:

Non-Allelic Homologous Recombination

NHEJ:

Non-Homologous End Joining

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Author information

Authors and Affiliations

  1. Department of Cancer Genetics, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias S/N, 4200-465, Porto, Portugal

    Hugo Pinheiro Ph.D. & Joana Carvalho Ph.D.

  2. Cancer Genetics Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias S/N, 4200-465, Porto, Portugal

    Carla Oliveira Ph.D.

  3. Faculty of Medicine, University of Porto, Porto, Portugal

    Carla Oliveira Ph.D.

Authors
  1. Hugo Pinheiro Ph.D.
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  2. Joana Carvalho Ph.D.
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  3. Carla Oliveira Ph.D.
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Corresponding author

Correspondence to Carla Oliveira Ph.D. .

Editor information

Editors and Affiliations

  1. Dept. of Medical, Surgical Sciences, and Neurosciences, University of Siena, viale Bracci, Siena, 53100, Italy

    Giovanni Corso

  2. Dept. of Medical, Surgical Sciences, and Neurosciences, University of Siena, Via Banchi di Sotto 55, Siena, 53100, Italy

    Franco Roviello

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Pinheiro, H., Carvalho, J., Oliveira, C. (2013). Alternative Mechanisms to Germline CDH1 Mutations in Hereditary Diffuse Gastric Cancer. In: Corso, G., Roviello, F. (eds) Spotlight on Familial and Hereditary Gastric Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6570-2_8

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