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Molecular and Biological Aspects of Microcephalin Gene: Directions in Brain Tumor and Methylation

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Epigenetics Territory and Cancer

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Abstract

Microcephalin gene (MCPH1) is located on chromosome 8p23.1 and initially was found to be involved in the pathogenesis of microcephaly. Its interaction with major cellular proteins especially cell cycle checkpoint molecules and DNA repair proteins demonstrated that it plays crucial roles in response to DNA damage and repair. In addition, some alterations have been detected in MCPH1 gene which led to name it as a new tumor suppressor gene. On the top, promoter methylation of MCPH1 gene and its direct effect on its protein expression has been proposed as a main mechanism of MCPH1 gene inactivation in various cancers especially brain tumors. Moreover, there are some reports that relying on the effect of MCPH1 gene mutations in development of non-cancerous diseases including neurocognitive disorders. In this chapter, at first the basics of MCPH1 gene and its protein will be described and then we will provide a brief literature of the investigations carried out on the role of MCPH1 gene alterations in various types of cancer and some other diseases. Moreover, the methylation data of our very recent research together with protein expression in brain tumors are provided.

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Abbreviations

AD::

Alzheimer disease

APC::

Anaphase promoting complex

ASD::

Autism spectrum disorders

ASPM::

Abnormal spindle microcephaly

ATM::

Ataxia telangiectasia mutated

ATR::

ATM and Rad3-related

BC::

Breast cancer

BIRT1::

BRCT—repeat inhibitor of human telomerase reverse transcriptase expression 1

BMI::

Body mass index

BRCT::

BRCA1 carboxyl-terminal

CDK5RAP2::

Cyclin-dependent kinase5 regulatory subunit associated protein 2

CENPJ::

Centromere protein J

CML::

Chronic myeloid leukemia

COBRA::

Combined bisulfite restriction analysis

DSB::

Double strand DNA break

EOC::

Epithelial ovarian cancer

GBM::

Gleioblastoma multiform

HCC::

Hepatocellular carcinoma

IF::

Immunofluorescence

LOH::

Loss of heterozygosity

MCPH1::

Microcephalin

MMR::

Mismatch repair

MR::

Mental retardation

MSI::

Microsatellite instability

MSP::

Methylation specific PCR

MSRA::

Methylation specific restriction analysis

NPCs::

Neural progenitor cells

NSCLC::

Non-small cell lung cancer

PCC::

Premature chromosome condensation

p53BP::

p53 binding protein

Q-FISH::

Quantitative—fluorescent in situ hybridization

OR::

Odds ratio

OSCC::

Oral squamous cell carcinoma

SNPs::

Single nucleotide polymorphisms

SSCP::

Single strand conformation polymorphism

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Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Keshavarz Boulevard, P.O. Box: 14176–13151, Tehran, Iran

    Fatemeh Karami & Prof. Dr. Parvin Mehdipour

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  1. Fatemeh Karami
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  2. Prof. Dr. Parvin Mehdipour
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Correspondence to Parvin Mehdipour .

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  1. Tehran University of Medical Sciences, Department of Medical Genetics School Of Medicine, Tehran, Iran

    Parvin Mehdipour

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Karami, F., Mehdipour, P. (2015). Molecular and Biological Aspects of Microcephalin Gene: Directions in Brain Tumor and Methylation. In: Mehdipour, P. (eds) Epigenetics Territory and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9639-2_7

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