Breast cancer genome heterogeneity: a challenge to personalised medicine?
- PMID: 21345264
- PMCID: PMC3109569
- DOI: 10.1186/bcr2807
Breast cancer genome heterogeneity: a challenge to personalised medicine?
Abstract
Implementation of high-throughput genomics sequencing approaches into routine laboratory practice has raised the potential for the identification of multiple breast cancer targets suitable for future therapeutic intervention in order to improve cancer outcomes. Results from these studies have revealed bewildering breast cancer genome complexity with very few aberrations occurring in common between breast cancers. In addition, such complexity is compounded by evidence of genomic heterogeneity occurring within individual breast cancers. Such inter-tumoural and intratumoural heterogeneity is likely to present a challenge to personalised therapeutic approaches that might be circumvented through the definition of genome instability mechanisms governing such diversity and their exploitation using synthetic lethal approaches.
References
-
- Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor GA, Teschendorff AE, Tse K, Turashvili G, Varhol R, Warren RL, Watson P, Zhao Y, Caldas C, Huntsman D, Hirst M, Marra MA, Aparicio S. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009;461:809–813. doi: 10.1038/nature08489. - DOI - PubMed
-
- Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED, Simpson JT, Stebbings LA, Leroy C, Edkins S, Mudie LJ, Greenman CD, Jia M, Latimer C, Teague JW, Lau KW, Burton J, Quail MA, Swerdlow H, Churcher C, Natrajan R, Sieuwerts AM, Martens JW, Silver DP, Langerod A, Russnes HE, Foekens JA, Reis-Filho JS, van't Veer L, Richardson AL, Borresen-Dale AL. et al.Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature. 2009;462:1005–1010. doi: 10.1038/nature08645. - DOI - PMC - PubMed
-
- Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Crowder R. et al.Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010;464:999–1005. doi: 10.1038/nature08989. - DOI - PMC - PubMed
-
- Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D, Lifshits E, Toschi L, Rogers A, Mok T, Sequist L, Lindeman NI, Murphy C, Akhavanfard S, Yeap BY, Xiao Y, Capelletti M, Iafrate AJ, Lee C, Christensen JG, Engelman JA, Janne PA. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010;17:77–88. doi: 10.1016/j.ccr.2009.11.022. - DOI - PMC - PubMed
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