High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer.
•Descargar como PPTX, PDF•
1 recomendación•704 vistas
Recomendados
Más contenido relacionado
La actualidad más candente
La actualidad más candente (20)
Similar a High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer.
Similar a High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer. (20)
Más de Raunak Shrestha
Más de Raunak Shrestha (12)
Último
Último (20)
High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer.
- 1. Raunak Shrestha Boyd et al., Genes Chromosomes Cancer. 2012 29 March 2012
- 2. BACKGROUND 2
- 3. Introduction • Prostate – an exocrine gland of the male reproductive system in most mammals • Plays a vital role during reproductive process • Prostate cancer occurs when cells in the prostate start to grow uncontrollably 3 http://upload.wikimedia.org/wikipedia/co mmons/a/a1/Prostatelead.jpg
- 4. ProstateCancer Prevalence • More common among men in North America than in Europe or Asia • most common cancer among Canadian men - it will afflict 1 in 7 elderly men 4 New Cases Deaths http://www.prostatecancer.ca/Prostate- Cancer/Prostate-Cancer/Prostate-Cancer-Facts Canadian Cancer Statistics 2011
- 5. Multifocality of Prostate Cancer • 50-75% of prostate cancer specimens contain more than one area or focus of cancer and called multifocal prostate cancer • generally consists of a dominant (or index) tumor and one or multiple separate smaller tumors 5 Andreoiu and Cheng, Human Pathology. 2010; Squire et al., Advances in Cancer Research. 2011 Monoclonal Origin Polyclonal Origin
- 6. Copynumberalterations (CNA)disrupt normalcellular behaviour • CNAs are segments of a chromosome ~1Kb to whole chromosomes where genetic material is lost or gained • CNAs are a hallmark of tumour genomes • CNAs can lead to adverse expression changes of targeted genes • Current Focus: find CNAs for diagnostics/prognostics, gene-disease association, targets for therapeutics 6 Chek (2005) Nature Sohrab Shah, Canadian Bioinformatics Workshop. 2010
- 7. METHODS 7
- 8. Tissue Sample Selection 8 • Fresh-frozen tissue from 18 males with prostate cancer • Histopathological techniques and Immuno-histochemistry techniques were used to find out various cancer lesions • High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) lesions were also distinguished from tumor lesions • 48 foci from 18 samples were selected for study Boyd et al., Genes Chromosomes Cancer. 2012
- 9. MeasurementTechnologies 9 Resolution FISH <10 Array CGH 30-100K Tech: #: Genotype arrays 100K-2M WGSS Sohrab Shah, Canadian Bioinformatics Workshop. 2010
- 10. Genotypingarrays - schematic 10 Sohrab Shah, Canadian Bioinformatics Workshop. 2010 • High density genotyping arrays: • Higher resolution (more loci) • Measurement of 2 alleles (Max. and Min. allele) at >1M loci
- 11. RESULTS 11
- 12. 12 • Identical genomic copy-number changes, shared by all same- case cancer foci and defined by the same breakpoints, were detected in 13 cases Boyd et al., Genes Chromosomes Cancer. 2012
- 13. 13 Boyd et al., Genes Chromosomes Cancer. 2012 • copynumber changes with identical breakpoints found in separate foci from the same case always affect the same allele
- 14. 14 Boyd et al., Genes Chromosomes Cancer. 2012
- 15. 15 Boyd et al., Genes Chromosomes Cancer. 2012
- 16. 16 • conserved genomic alterations in majority of the cases suggesting monoclonal origin Boyd et al., Genes Chromosomes Cancer. 2012
- 17. Conclusion • From previous molecular studies in prostate cancer, polyclonal origin is widely believed • But these studies assume that, for foci to be monoclonal, same case foci must share all genetic alterations • Passenger mutations outnumber the Driver mutations • Passenger mutations accumulate in cancer subclones independently and may not be common to all the subclones (or to all foci) 17
- 18. Conclusion • This paper hypothesize that, • if foci were monoclonal in origin, all same-case foci would share some early genetic changes, with conserved breakpoints, • individual foci from that case would harbor additional genetic changes acquired during subclonal progression. • But does not completely rule out the polyclonal origin • Though majority of cases exhibited monoclonal origin small fraction of cases did not fit into this model !!! • Study recommends further study with larger sample size 18
- 19. Critiques • Analyzed only the copy-number changes to study the clonal origin of the multifocal cancers • Sequence level variation as well as other Genomic Variation could give more insight on the topic • Did not use the sequence information of the cancer genome to look for precise breakpoints in the genome • DNA extraction from the micro-dissected tissue samples would be very difficult • DNA concentration may not be well enough for sequencing 19
- 20. 20 ? Questions