Olufunmilayo Olopade, M.D.

Molecular Genetics of Breast Cancer, Tumor Suppressor Genes, Mechanisms of Oncogene Amplification

Research Summary

We are interested in the cloning and characterization of a putative tumor suppressor gene (TSG9) on the short arm of chromosome 9 (9p21). Identification of the TSG9 will be of particular significance in human cancer because this region on 9p is frequently deleted in a wide variety of tumor types. We have assembled a 2.8 megayac contig within the critical region on 9p21 and have isolated several cDNAs which are now being analyzed for their role as candidate TSGs. One candidate gene, CDKN2, has recently been mapped to this region. CDKN2 is involved in cell cycle regulation by functioning as an inhibitor of CDK4 in transformed cells. We are reintroducing the deleted part of 9p into human cell lines by transfection in order to study the effects of restoring the TSG9 on the transformed phenotype and to study its possible interactions with other genes involved in cell growth and differentiation. Our studies should reveal alterations in this TSG9 in solid tumors especially glioma, lung, bladder and breast cancers.

Selected Papers

Fackenthal JD, Cartegni L, Krainer AR, Olopade OI. (2002). BRCA2 T2722R is a deleterious allele that causes exon skipping.Am J Hum Genet. 71(3):625-31. Epub 2002 Jul 19. Erratum in: Am J Hum Genet. 73(6):1477.

Grushko TA, Blackwood MA, Schumm PL, Hagos FG, Adeyanju MO, Feldman MD, Sanders MO, Weber BL, Olopade OI.
(2002). Molecular-cytogenetic analysis of HER-2/neu gene in BRCA1-associated breast cancers.Cancer Res. 62(5):1481-8.

Olopade OI, Wei M. (2003). FANCF methylation contributes to chemoselectivity in ovarian cancer. Cancer Cell. 3(5):417-20. Review.

Grushko TA, Dignam JJ, Das S, Blackwood AM, Perou CM, Ridderstrale KK, Anderson KN, Wei MJ, Adams AJ, Hagos FG, Sveen L, Lynch HT, Weber BL, Olopade OI. (2004). MYC is amplified in BRCA1-associated breast cancers. Clin Cancer Res. 10(2):499-507.

Medved M, Newstead GM, Abe H, Zamora MA, Olopade OI, Karczmar GS. (2006). High spectral and spatial resolution MRI of breast lesions: preliminary clinical experience. AJR Am J Roentgenol. 186(1):30-7.

Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM. (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 19(2):264-71.

Domchek SM, Friebel TM, Neuhausen SL, Wagner T, Evans G, Isaacs C, Garber JE, Daly MB, Eeles R, Matloff E, Tomlinson GE, Van't Veer L, Lynch HT, Olopade OI, Weber BL, Rebbeck TR. (2006) Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study.Lancet Oncol. 7(3):223-9.

Friedman E, Kotsopoulos J, Lubinski J, Lynch HT, Ghadirian P, Neuhausen SL, Isaacs C, Weber B, Foulkes WD, Moller P, Rosen B, Kim-Sing C, Gershoni-Baruch R, Ainsworth P, Daly M, Tung N, Eisen A, Olopade OI, Karlan B, Saal HM, Garber JE, Rennert G, Gilchrist D, Eng C, Offit K, Osborne M, Sun P, Narod SA. (2006). Hereditary Breast Cancer Clinical Study Group. Spontaneous and therapeutic abortions and the risk of breast cancer among BRCA mutation carriers.Breast Cancer Res. 8(2):R15.

Olopade OI. (2006). Using genetic analysis to individualize preventive measures for breast and ovarian cancers.Nat Clin Pract Oncol. 3(4):182-3.

Bradbury A, Olopade OI. (2006). The case for individualized screening recommendations for breast cancer.J Clin Oncol. 24(21):3328-30. Epub 2006 Jun 26.

Salant T, Ganschow PS, Olopade OI, Lauderdale DS. (2006). "Why take it if you don't have anything?" breast cancer risk perceptions and prevention choices at a public hospital.J Gen Intern Med. 21(7):779-85.

Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, Murphy J, Ghadirian P, Friedman E, Foulkes WD, Kim-Sing C, Wagner T, Tung N, Couch F, Stoppa-Lyonnet D, Ainsworth P, Daly M, Pasini B, Gershoni-Baruch R, Eng C, Olopade OI, McLennan J, Karlan B, Weitzel J, Sun P, Narod SA. (2006). Hereditary Ovarian Cancer Clinical Study Group. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation.JAMA. 296(2):185-92.

Locker GY, Kaul K, Weinberg DS, Gatalica Z, Gong G, Peterman A, Lynch J, Klatzco L, Olopade OI, Bomzer CA, Newlin A, Keenan E, Tajuddin M, Knezetic J, Coronel S, Lynch HT. (2006). The I1307K APC polymorphism in Ashkenazi Jews with colorectal cancer: clinical and pathologic features.Cancer Genet Cytogenet. 169(1):33-8.

Hall MJ, Li L, Wiernik PH, Olopade OI. (2006). BRCA2 mutation and the risk of hematologic malignancy.Leuk Lymphoma. 47(4):765-7.

Kodl MM, Lee JW, Matthews AK, Cummings SA, Olopade OI. (2006). Correlates of depressive symptoms among women seeking cancer genetic counseling and risk assessment at a high-risk cancer clinic. J Genet Couns. 15(4):267-76.

Fan X, Abe H, Medved M, Foxley S, Arkani S, Zamora MA, Olopade OI, Newstead GM, Karczmar GS. (2006). Fat suppression with spectrally selective inversion vs. high spectral and spatial resolution MRI of breast lesions: qualitative and quantitative comparisons.J Magn Reson Imaging. 24(6):1311-5.