Kevin Brown, Ph.D.

Investigator

Kevin Brown, Ph.D.

Organization:	National Cancer Institute Division of Cancer Epidemiology & Genetics, Laboratory of Translational Genomics
Address:	8717 Grovemont Circle ATC Room 152H
Phone:	301-435-2414
Fax:	301-402-3134
E-mail:	brownkm2@mail.nih.gov

Biography
Research Interests
Selected Publications
NCI Publications (Text and abstracts from the DCEG publications database)
Brown Lab Members

Biography

Dr. Brown received a Ph.D. in Genetics from George Washington University in Washington, D.C. in 2003. He conducted his post-doc training at the Translational Genomic Research Institute in Phoenix, Arizona. In his position as an investigator at the Translational Genomic Research Institute, Dr. Brown has worked on studies using whole-genome familial linkage, candidate gene, and genome-wide association approaches to identify genetic variants associated with melanoma susceptibility. His lab has also used high-throughput functional genomics to investigate genes associated with therapeutic sensitivity and resistance in melanoma. Dr. Brown has served as an adjunct professor at the Mayo Clinic Cancer Center in basic medical sciences, the University of Arizona College of Medicine and Arizona State University.

Research Interests

Germline cancer genetics

My research is focused on identifying the genetic contributions and functional pathways associated with cancer risk. While early-stage melanoma is largely curable via surgical resection, late-stage melanoma remains nearly incurable despite decades of research. Much of the effort in my laboratory is directed towards better understanding genetic factors contributing to melanoma risk, with a goal of ultimately facilitating prevention and early-detection efforts in at-risk individuals. Collaborations with studies in the United Kingdom and Australia are underway to identify variants in melanoma-specific oncogenes and understand the functional pathways related to transcriptional activity of these oncogenes. My lab also focuses on the genetics of melanoma susceptibility in melanoma families. Familial linkage studies have identified a locus on chromosome band 1p22. However, these studies demonstrate that in families, melanoma risk is heterogeneous and is likely explained by a combination of rare high-penetrance loci as well as common, low-penetrance loci.

Somatic cancer genetics and therapeutic applications

My research interests also extend to the downstream therapeutic applications of melanoma genome-wide association studies (GWAS). My laboratory is engaged in large-scale RNAi drug sensitization screening efforts with the aim of identifying molecularly-informed combination therapies to move into preclinical and clinical testing. The first step of this process has been to fully characterize somatic patterns of loss within the chromosome band 1p22 melanoma susceptibility region. We have since expanded our efforts and generated an in-house panel of over 70 well-characterized melanoma cell lines for use as a screening resource in the area of melanoma therapeutics.

Methodology

Dr. Brown and colleagues have recently developed VEGAS, a Versatile Gene-based Test for GWAS. This new approach is applicable to GWAS study designs where permutation-based approaches are not possible. VEGAS is applicable to family-based GWAS, GWAS meta-analysis and data-pooling-based GWAS. For more information, see VEGAS: versatile gene-based tests for genome-wide association studies.

Consortiums

International Melanoma Genetics Consortium (GenoMEL), Pancreatic Cancer Genetics and Epidemiology Consortium (PACGENE), Canine Hereditary Cancer Consortium (CHCC), Melanoma Post-GWA Consortium (MPGC)

Selected Publications

Yokoyama S, Woods SL, Boyle GM, Aoude LG, MacGregor S, Zismann V, Gartside M, Cust AE, Haq R, Harland M, Taylor J, Duffy DL, Holohan K, Dutton-Regester K, Palmer JM, Bonazzi V, Stark MS, Symmons J, Law MH, Schmidt C, Lanagan C, O’Connor L, Holland EA, Schmid H, Maskiell JA, Jetann J, Ferguson M, Jenkins MA, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Whiteman DC, Pharoah PD, Easton DF, Dunning AM, Newton-Bishop JA, Montgomery GW, Martin NG, Mann GJ, Bishop DT, Tsao H, Trent JM, Fisher DE, Hayward NK, Brown KM. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 2011 Nov 13;480(7375):99-103.
MacGregor S, Montgomery GW, Liu JZ, Zhao ZZ, Henders AK, Stark M, Schmid H, Holland EA, Duffy DL, Zhang M, Painter JN, Nyholt DR, Maskiell JA, Jetann J, Ferguson M, Cust AE, Jenkins MA, Whiteman DC, Olsson H, Puig S, Bianchi-Scarrà G, Hansson J, Demenais F, Landi MT, Debniak T, Mackie R, Azizi E, Bressac B, Goldstein AM, Kanetsky PA, Gruis NA, Elder DE, Newton Bishop JA, Bishop DT, Iles MM, Helsing P, Amos CI, Wei Q, Wang LE, Lee JE, Qureshi AA, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Han J, Hopper JL, Trent JM, Brown KM, Martin NG, Mann GJ, Hayward NK. Two novel loci for melanoma susceptibility on chromosome bands 1q42.12 and 1q21.3.Nature Genetics 2011 Oct 9;43(11):1114-8.
Barrett JH, Iles MM, Harland M, Taylor JC, Snowden H, Randerson-Moor J, Corda E, Andresen PA, Akslen LA, Avril M, Azizi E, Bakker B, Bianchi-Scarra G, Bressac B, Calista D, Cannon-Albright L, Debniak T, Duffy D, Dunning A, Easton DF, Friedman E, Galan P, Ghiorzo P, Hansson J, Helsing P, Hocevar M, Hojom V, Ingvar C, Janssen B, Landi MT, Lang J, Lubinski J, Mackie R, Martin N, Molern A, Montgomery G, van Nieuwpoort FA, Novakovic S, Olsson H, Puig S, Puig-Butille JA, van der Stoep N, Whiteman D, Zelenika D, Lathrop M, Gillanders E, Brown KM, Goldstein AE, Kanetsky PA, Mann G, MacGregor S, Elder DE, Gruis NA, Amos C, Hayward N, Demenais F, Newton Bishop J, Bishop DT. Novel melanoma loci suggest a pathway independent of pigmentation and nevus phenotype.Nature Genetics 2011 Oct 9;43(11):1108-13.
Amos CI, Wang LE, Lee JE, Gershenwald JE, Chen WV, Fang S, Kosoy R, Zhang M, Qureshi AA, Vattathil S, Schacherer CW, Gardner JM, Wang Y, Bishop DT, Barrett JH, GenoMEL Investigators, MacGregor S, Hayward NK, Martin NG, Duffy DL, Q-Mega Investigators, Mann GJ, Cust A, Hopper J, AMFS Investigators, Brown KM, Grimm EA, Xu Y, Han Y, Jing K, McHugh C, Laurie CC, Doheny KF, Pugh EW, Seldin MF, Han J, Wei Q. Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.Human Molecular Genetics 2011 Dec 15;20(24):5012-23. Epub 2011 Sep 17.
Conde L, Halperin E, Akers NK, Brown KM, Smedby KE, Rothman N, Nieters A, Slager SL, Brooks-Wilson A, Agana L, Riby J, Liu J, Adami HO, Darabi H, Hjalgrim H, Low HQ, Humphreys K, Melbye M, Chang ET, Glimelius B, Cozen W, Davis S, Hartge P, Morton LM, Schenk M, Wang SS, Armstrong B, Kricker A, Milliken S, Purdue MP, Vajdic CM, Boyle P, Lan Q, Zahm SH, Zhang Y, Zheng T, Becker N, Benavente Y, Boffetta P, Brennan P, Butterbach K, Cocco P, Foretova L, Maynadié M, de Sanjosé S, Staines A, Spinelli JJ, Achenbach SJ, Call TG, Camp NJ, Glenn M, Caporaso NE, Cerhan JR, Cunningham JM, Goldin LR, Hanson CA, Kay NE, Lanasa MC, Leis JF, Marti GE, Rabe KG, Rassenti LZ, Spector LG, Strom SS, Vachon CM, Weinberg JB, Holly EA, Chanock S, Smith MT, Bracci PM, Skibola CF. Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32. Nature Genetics 2010 Aug;42(8):661-4. Epub 2010 Jul 18
Skibola CF, Bracci PM, Halperin E, Conde L, Craig DW, Agana L, Iyadurai K, Becker N, Brookes-Wilson A, Curry JD, Spinelli JJ, Holly EA, Riby J, Zhang L, Nieters A, Smith MT, Brown KM. Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma. Nature Genetics 2009, 41(8):873-5
Brown KM, MacGregor S, Montgomery GW, Craig DW, Zhao Z, Iyadurai K, Henders A, Homer N, Campbell M, Stark M, Thomas S, Schmid H, Holland EA, Gillanders EM, Duffy DL, Maskiell JA, Jetann J, Ferguson M, Stephan DA, Cust AE, Whiteman D, Green A, Olsson H, Puig S, Ghiorzo P, Hansson J, Demenais F, Goldstein AM, Gruis NA, Elder DE, Newton-Bishop J, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Martin NG, Trent JM, Mann GJ, Hayward NK. Common sequence variants on 20q11.22 confer melanoma susceptibility. Nature Genetics 2008, 40(7):838-40