Research

Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha

Luigi Scotto¹ , Gopeshwar Narayan^1,2 , Subhadra V Nandula¹ , Shivakumar Subramaniyam¹ , Andreas M Kaufmann³ , Jason D Wright⁴ , Bhavana Pothuri^4,5 , Mahesh Mansukhani¹ , Achim Schneider³ , Hugo Arias-Pulido^6,7 and Vundavalli V Murty^1,8,9

¹Department of Pathology, Columbia University Medical Center, New York, New York, USA

²Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India

³Department of Gynecology, Charité Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin, Germany

⁴Gynecologic Oncology, Columbia University Medical Center, New York, New York, USA

⁵Department of Gyenecologic Oncology, New York University Medical Center, New York, New York, USA

⁶Division of Hematology/Oncology, The University of New Mexico Cancer Center, 900 Camino de Salud NE, Albuquerque, New Mexico, USA

⁷Department of Tumor Molecular Biology, Instituto Nacional de Cancerología, Bogotá, Colombia

⁸Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA

⁹Irving Cancer Research Center, Room 605, Columbia University Medical Center, 1130 St. Nicholas Ave, New York, New York 10032, USA

author email corresponding author email

Molecular Cancer 2008, 7:58doi:10.1186/1476-4598-7-58

Published:	17 June 2008

Abstract

Background

Copy number gains and amplifications are characteristic feature of cervical cancer (CC) genomes for which the underlying mechanisms are unclear. These changes may possess oncogenic properties by deregulating tumor-related genes. Gain of short arm of chromosome 5 (5p) is the most frequent karyotypic change in CC.

Methods

To examine the role of 5p gain, we performed a combination of single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression analyses on invasive cancer and in various stages of CC progression.

Results

The SNP and FISH analyses revealed copy number increase (CNI) of 5p in 63% of invasive CC, which arises at later stages of precancerous lesions in CC development. We integrated chromosome 5 genomic copy number and gene expression data to identify key target over expressed genes as a consequence of 5p gain. One of the candidates identified was Drosha (RNASEN), a gene that is required in the first step of microRNA (miRNA) processing in the nucleus. Other 5p genes identified as targets of CNI play a role in DNA repair and cell cycle regulation (BASP1, TARS, PAIP1, BRD9, RAD1, SKP2, and POLS), signal transduction (OSMR), and mitochondrial oxidative phosphorylation (NNT, SDHA, and NDUFS6), suggesting that disruption of pathways involving these genes may contribute to CC progression.

Conclusion

Taken together, we demonstrate the power of integrating genomics data with expression data in deciphering tumor-related targets of CNI. Identification of 5p gene targets in CC denotes an important step towards biomarker development and forms a framework for testing as molecular therapeutic targets.