Molecular cytogenetic evidence for multistep tumorigenesis: Implications for risk assessment and early detection

Issue title: Translational Pathology of Early Cancer

Guest editors: Sudhir Srivastavax and William E. Grizzley

Article type: Research Article

Authors: Sen, Subrata^{a; b; *} | Hopwood, Vicki^c

Affiliations: [a] Department of Molecular Pathology, Division of Pathology and Laboratory Medicine, Houston, TX, USA | [b] Program in Human and Molecular Genetics, Graduate school of Biomedical Sciences, Houston, TX, USA | [c] Cytogenetic Technology Program, School of Health Professions, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA | [x] Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA | [y] Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: [*] Corresponding author: Subrata Sen, Department of Molecular Pathology, Unit 951, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, 7435 Fannin St., Houston, Texas 77054, USA. Tel.: +1 713 834 6040; Fax: +1 713 834 6083. E-mail: [email protected].

Abstract: There is strong evidence that multistep tumorigenesis begins with the acquisition of somatic mutations which promote genomic instability. Genomic instability is an important malignant trait because genomic instability can generate the genetic diversity that is necessary for the transforming cell to acquire increasingly variable and aggressive tumor phenotypes. Genomic instability often manifests in the form of chromosomal instability (CIN) leading to the induction of aneuploidy, a phenomenon identified by high resolution molecular cytogenetic techniques. Fluorescent in situ hybridization (FISH) and Array Comparative Genomic Hybridization (aCGH) are two high resolution molecular cytogenetic techniques that allow detection of chromosomal aneuploidy and structural rearrangements occurring in pre-malignant and malignant lesions during tumor progression and invasion. These high resolution molecular cytogenetic techniques are used for genetic screening of single cells in pre-malignant and precursor malignant lesions as well as in exfoliated cells from body fluids and excreta. Consequently, molecular cytogenetic testing offers the promise of an extremely powerful method of risk assessment and early detection of cancer.

Keywords: Chromosomal instability (CIN), aneuploidy, genetic mutation, microenvironment, chromosomal rearrangements, gene amplification, gene fusion, chromosome deletion, spindle assembly checkpoint, Fluorescence in situ hybridization (FISH), Array Comparative Genomic Hybridization (aCGH)

DOI: 10.3233/CBM-2011-0171

Journal: Cancer Biomarkers, vol. 9, no. 1-6, pp. 113-132, 2011