Open Access Open Badges Research article

Potential contribution of SIM2 and ETS2 functional polymorphisms in Down syndrome associated malignancies

Arpita Chatterjee1, Samikshan Dutta16, Sanjit Mukherjee2, Nupur Mukherjee3, Avirup Dutta2, Ashis Mukherjee4, Swagata Sinha1, Chinmay Kumar Panda3, Keya Chaudhuri2, Ananda L Roy5 and Kanchan Mukhopadhyay1*

Author affiliations

1 Manovikas Biomedical Research and Diagnostic Centre, MRIH, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India

2 Indian Institute of Chemical Biology, Kolkata, India

3 Chittaranjan National Cancer Institute, Kolkata, India

4 Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India

5 Tufts University School of Medicine, Boston, MA, USA

6 Present address: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Nebraska, USA

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Citation and License

BMC Medical Genetics 2013, 14:12  doi:10.1186/1471-2350-14-12

Published: 23 January 2013



Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer (OC), show rare incidences. Triplication of the human chromosome 21 in DS is associated with altered genetic dosage of different TFs. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and Single Minded 2 (SIM2) are two such TFs that regulate several downstream genes involved in developmental and neurological pathways. Here we studied functional genetic polymorphisms (fSNP) in ETS2 and SIM2 encoding genes in a group of patients and control subjects to better understand association of these variants with DS phenotypes.


We employed an in silico approach to identify potential target pathways of ETS2 and SIM2. fSNPs in genes encoding for these two TFs were identified using available databases. Selected sites were genotyped in individuals with DS, their parents, ALL, BC, OC as well as ethnically matched control individuals. We further analyzed these data by population-based statistical methods.


Allelic/genotypic association analysis showed significant (P < 0.03) differences of rs2070530, rs1051476, rs11254, rs711 for DS subjects compared to control. rs711 also exhibited significantly different genotypic distribution pattern in parents of DS probands (P < 0.02) and BC patients (P < 0.02). Interaction analysis revealed independent main effect of rs711 in all the groups, while rs11254 exhibited independent main effect in DS subjects only. High entropy values were noticed for rs461155 in the solid tumor groups. Significant interactive effects of rs2070531 with rs1051475, rs1051476, rs11254 were observed in all the groups except DS.


We infer from the present investigation that the difference in frequencies of fSNPs and their independent as well as interactive effects may be the cause for altered expression of SIM2 and ETS2 in DS and malignant groups, which affects different downstream biological pathways. Thus, altered expression of SIM2 and ETS2 could be one of the reasons for variable occurrence of different malignant conditions in DS.

SIM2; ETS2; Down syndrome; Breast cancer; Oral cancer; Acute lymphoblastic leukemia