b'Redefining Research & Caretumors may include paragangliomas and pheochromocytomas (adre-nal gland).Tuberous sclerosis complex (genes: TSC1, TSC2) presents an increased risk for RCC. Other tumors include angiomyolipomas (kidney) and benign brain tumors (subependymal giant cell astrocytomas). Additional features include skin and nail lesions, kidney cysts, and lung abnormalities.Holistic CareDesignated by the VHL Alliance as a Clinical Care Center, UT Southwestern provides holistic care to patients with familial kidney cancer syndromes such as VHL, HPRCC, BHD, and HLRCC. A NEW HEREDITARYKIDNEY CANCER SYNDROME Partners inWhile many familial kidney cancers areThese individuals had a predispositionhad defective BAP1. Today, testingInternational Collaborationaccounted for by the genes aforemen- to kidney cancer that could not befor the gene is performed routinely in tioned, the gene remains unknownexplained by well-established genes.families with a hereditary risk of kid- (Dana-Farber Cancer Institute). how treatments developed for ccRCC in some families. Dr. Brugarolas andInvestigators identified one familyney cancer. (Farley et al., Mol CancerThe Kidney Cancer Program collaboratesThe consortiums database housesimpact less frequent tumor types (such colleagues, after discovering that thewhose members with kidney cancerRes, 2013) with scientists worldwide.demographic, pathologic, laboratory, andas nccRCC). BAP1 gene is mutated in sporadictreatment information on more than 6,000UT Southwestern scientists have co- (non-hereditary) clear cell RCC (seeTeaming with dozens of institutions withpatients. UT Southwestern has contributedauthored several publications under the Tree of a family with BAP1 page 40), asked whether BAP1 muta- mutation. People who developedrobust kidney cancer programs arounddata on more than 350 patients with meta- consortium umbrella, including papers tions could also account for cases ofI:1 I:2 kidney cancer appear in pink. the world, the Kidney Cancer Program isstatic RCC. characterizing metastatic papillary RCC, familial kidney cancer. helping reshape medicines understand- Collectively, the information has resultedand honing prognostic accuracy and drug Previously, BAP1 mutations hading of the disease. The partnership isin more than 50 scientific publications.selection for patients beginning second-line been discovered in the germline andcalled the International Metastatic RenalResearchers have pinpointed factorstherapy. (Wells et al., Cancer Med, 2017; De found to be associated with skin andCell Carcinoma Database Consortiumassociated with prognosis, evaluated howVelasco et al., Clin Genitourin Cancer, 2017; eye cancer (melanoma), cancer of the(IMDC) and is led by Dr. Daniel Hengdifferent sequences of treatments affectDavis et al., Eur Urol, 2017; Wells et al., Eur lung outer lining (mesothelioma), andII:1 II:2 II:3 II:4 II:5 II:6 II:7 II:8 (University of Calgary) and Dr. Toni Choueirioutcomes, and provided information aboutUrol, 2017)other cancers including kidney cancer. Whether they could account for cases of familial kidney cancer where there were no other features was unknown. SOME COUNTRIES REPRESENTED IN THE IMDCIn a collaboration including the National Cancer Institute, ClevelandIII:1 III:2 III:3 III:4 III:5 III:6Clinic, and UT Health Science CenterBELGIUMSan Antonio, UT Southwestern investi- AUSTRALIA BELGIUM CANADA DENMARK GREECE ITALYgators sequenced BAP1 in individualsRCCfrom 83 families in a study partly funded by CPRIT (Cancer PreventionBAP1 POLANDand Research Institute of Texas).Mutation Positive IV:1 IV:4 IV:6JAPAN POLAND SINGAPORE SOUTH KOREA SPAIN UNITED STATES60 61'