Abstract

Intratumor heterogeneity (ITH) plays a crucial role in tumor evolution, treatment response, and disease prognostication. We have developed a FISH based approach to enumerate gene and chromosomal copy number changes in single interphase nuclei (miFISH) of primary tumors and derived cell lines. This approach is based on the sequential hybridization of cancer relevant probes. The multiplex hybridization of these probes allows enumeration of up to 20 loci in individual cancer cells, therefore providing a comprehensive picture of ITH. The microscope system, automated image acquisition and signal enumeration was developed with the company BioView (Rehovot, Israel). In collaboration with Drs. Alejandro Schaeffer and E. Michael Gertz (both NCBI) and Dr. Russell Schwartz (Carnegie Mellon University, Pittsburgh, PA) we developed an algorithm that allows interpretation of the complex data sets, termed FISHtres. FISHtrees has been applied for the analysis of genome dynamics of breast, prostate, colorectal, head and neck, and cervical carcinomas, their precursor lesions, and derived cell lines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010834-11
Application #
9556383
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Rausch, Valentin; Krieg, Andreas; Camps, Jordi et al. (2017) Array comparative genomic hybridization of 18 pancreatic ductal adenocarcinomas and their autologous metastases. BMC Res Notes 10:560
McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O et al. (2017) Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas. Genes Chromosomes Cancer 56:199-213
Gertz, E Michael; Chowdhury, Salim Akhter; Lee, Woei-Jyh et al. (2016) FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe. PLoS One 11:e0158569
Wangsa, Darawalee; Chowdhury, Salim Akhter; Ryott, Michael et al. (2016) Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis. Int J Cancer 138:98-109
Gemoll, Timo; Auer, Gert; Ried, Thomas et al. (2015) Genetic Instability and Disease Prognostication. Recent Results Cancer Res 200:81-94
Chowdhury, Salim Akhter; Gertz, E Michael; Wangsa, Darawalee et al. (2015) Inferring models of multiscale copy number evolution for single-tumor phylogenetics. Bioinformatics 31:i258-67
Hathcock, Karen S; Padilla-Nash, Hesed M; Camps, Jordi et al. (2015) ATM deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma in humans. Blood 126:2291-301
Akagi, Keiko; Li, Jingfeng; Broutian, Tatevik R et al. (2014) Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res 24:185-99
Chowdhury, Salim Akhter; Shackney, Stanley E; Heselmeyer-Haddad, Kerstin et al. (2014) Algorithms to model single gene, single chromosome, and whole genome copy number changes jointly in tumor phylogenetics. PLoS Comput Biol 10:e1003740
Kirshenbaum, Arnold S; Petrik, Amy; Walsh, Rosemary et al. (2014) A ten-year retrospective analysis of the distribution, use and phenotypic characteristics of the LAD2 human mast cell line. Int Arch Allergy Immunol 164:265-70

Showing the most recent 10 out of 32 publications