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Alterations of ATM and CADM1 in Chromosomal 11q22.3–23.2 Region are Associated with the Development of Invasive Cervical Carcinoma.

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Title Alterations of ATM and CADM1 in Chromosomal 11q22.3–23.2
Region are Associated with the Development of Invasive Cervical Carcinoma.
 
Creator Mazumder Indra, Dipanjana
Mitra, Sraboni
Roy, Anup
Mondal, Ranajit Kumar
Basu, Partha Sarathi
Roychoudhury, Susanta
Chakravarty, Runu
Panda, Chinmay Kumar
 
Subject Molecular & Human Genetics
 
Description To understand the importance of chr11q22.3–
23.2 region in the development of cervical cancer, we have
studied the genetic and epigenetic alterations of the candidate
genes ATM, PPP2R1B, SDHD and CADM1 in cervical
intraepithelial neoplasia (CIN) and cervical carcinoma
(CACX) samples. Our study revealed low expression and
high alterations (methylation/deletion) (55–59%) of ATM
and CADM1 genes along with poor patient outcome. The
alterations of ATM and CADM1 are associated with the
progression of tumor from CIN to Stage I/II, thus implying
their role in early invasiveness. The two genes, PPP2R1B
and SDHD, lying in between ATM and CADM1, have low
frequency of alterations, and majority of the alterations
are in CACX samples, indicating that their alterations might be associated with disease progression. Expressions (mRNA/
protein) of the genes showed concordance with their
molecular alterations. Significant co-alteration of ATM and
CADM1 points to their synergic action for the development
of CACX. Mutation is, however, a rare phenomenon for
inactivation of ATM. Association between the alteration of
ATM and CHEK1 and poor survival of the patients having
co-alterations of ATM and CHEK1 points to the DNA
damage response pathway disruption in development
of CACX. Thus, our data suggest that inactivation of
ATM–CHEK1-associated DNA damage response pathway
and CADM1-associated signaling network might have an
important role in the development of CACX
.
 
Publisher Springer Verlag
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1268/1/HUMAN_GENETICS__130(_6)735%2D748;2011[8].pdf
Mazumder Indra, Dipanjana and Mitra, Sraboni and Roy, Anup and Mondal, Ranajit Kumar and Basu, Partha Sarathi and Roychoudhury, Susanta and Chakravarty, Runu and Panda, Chinmay Kumar (2011) Alterations of ATM and CADM1 in Chromosomal 11q22.3–23.2 Region are Associated with the Development of Invasive Cervical Carcinoma. Human Genetics, 130 (6). pp. 735-748.
 
Relation http://dx.doi.org/10.1007/s00439-011-1015-8
http://www.eprints.iicb.res.in/1268/