HotSpotter: efficient visualization of driver mutations

BMC Genomics

Scott E Woodman¹  Jason Roszik¹ 

[1] Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 7455 Fannin St, Houston, TX 77054, USA

关键词: Visualization;    Hotspots;    Driver mutation;    Cancer;   

Others  :  1090256
DOI  :  10.1186/1471-2164-15-1044

 received in 2014-07-11, accepted in 2014-11-12,  发布年份 2014

【 摘 要 】

Background

Driver mutations are positively selected during the evolution of cancers. The relative frequency of a particular mutation within a gene is typically used as a criterion for identifying a driver mutation. However, driver mutations may occur with relative infrequency at a particular site, but cluster within a region of the gene. When analyzing across different cancers, particular mutation sites or mutations within a particular region of the gene may be of relatively low frequency in some cancers, but still provide selective growth advantage.

Results

This paper presents a method that allows rapid and easy visualization of mutation data sets and identification of potential gene mutation hotspot sites and/or regions. As an example, we identified hotspot regions in the NFE2L2 gene that are potentially functionally relevant in endometrial cancer, but would be missed using other analyses.

Conclusions

HotSpotter is a quick, easy-to-use visualization tool that delivers gene identities with associated mutation locations and frequencies overlaid upon a large cancer mutation reference set. This allows the user to identify potential driver mutations that are less frequent in a cancer or are localized in a hotspot region of relatively infrequent mutations.

【 授权许可】

   
2014 Roszik and Woodman; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Stratton MR, Campbell PJ, Futreal PA: The cancer genome. Nature 2009, 458(7239):719-724.
• [2]Zhang J, Liu J, Sun J, Chen C, Foltz G, Lin B: Identifying driver mutations from sequencing data of heterogeneous tumors in the era of personalized genome sequencing. Brief Bioinform 2013. in press
• [3]Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L: Mutational landscape and significance across 12 major cancer types. Nature 2013, 502(7471):333-339.
• [4]Woodman SE, Lazar AJ, Aldape KD, Davies MA: New strategies in melanoma: molecular testing in advanced disease. Clinical cancer research: an official journal of the American Association for Cancer Research 2012, 18(5):1195-1200.
• [5]Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, Hamid O, Infante JR, Millward M, Pavlick AC, O'Day SJ, Blackman SC, Curtis CM, Lebowitz P, Ma B, Ouellet D, Kefford RF: Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 2012, 379(9829):1893-1901.
• [6]COSMIC: Catalogue of somatic mutations in cancer. http://cancer.sanger.ac.uk/files/cosmic/current_release webcite
• [7]Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N: The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer discovery 2012, 2(5):401-404.
• [8]Goldman M, Craft B, Swatloski T, Ellrott K, Cline M, Diekhans M, Ma S, Wilks C, Stuart J, Haussler D, Zhu J: The UCSC Cancer Genomics Browser: update 2013. Nucleic Acids Res 2013, 41(Database issue):D949-D954.
• [9]TCGA: The Cancer Genome Atlas. http://cancergenome.nih.gov webcite
• [10]Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA, Cancer Genome Atlas Research Network: Integrated genomic characterization of endometrial carcinoma. Nature 2013, 497(7447):67-73.
• [11]Sasaki H, Hikosaka Y, Okuda K, Kawano O, Moriyama S, Yano M, Fujii Y: NFE2L2 gene mutation in male Japanese squamous cell carcinoma of the lung. J ThorAcic Oncol 2010, 5(6):786-789.
• [12]Tableau : Software Inc. Tableau Desktop. http://www.tableausoftware.com/products/desktop webcite