Pinto E.M.,Outreach |
Pinto E.M.,St Jude Childrens Research Hospital |
Ribeiro R.C.,Outreach |
Ribeiro R.C.,St Jude Childrens Research Hospital |
And 10 more authors.
Oncogenesis | Year: 2012
Most inherited TP53 mutations have been identified in individuals with a family cancer predisposition syndrome, in which the activity of p53 mutants is severely reduced. However, germline p53 mutants in children with sporadic adrenocortical or choroid plexus tumors exhibit a wide range of functional activity. Here, we demonstrate the occurrence of a complex germline TP53 mutation in two unrelated families with different cancer phenotypes, neither fulfilling the classic criteria for Li-Fraumeni syndrome. The TP53 mutation consists of a duplication of 7 bp in exon 4, resulting in a frame shift and premature stop signal. Haplotype analysis indicated that the mutation arose independently in the two families. Analysis of the DNA secondary structure predicts the TP53 mutation occurred within a hairpin loop. Additional germline complex mutations occurring within the same region of exon 4 have been identified in the IARC database. Our findings suggest that certain TP53 regions are prone to intrinsic genetic alterations, possibly through defects in DNA replication or repair. Further, carriers of the same TP53 mutation can have diverse cancer profiles, illustrating the complexity of genetic counseling and risk prediction. © 2012 Macmillan Publishers Limited All rights reserved.
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: HEALTH-2007-4.1-8 | Award Amount: 855.80K | Year: 2009
The iNTER Support Action (iSA) Project aims to create a pilot cooperative medical support network constituted by the Hospital Son Espases (former Son Dureta) (Spain), the Instituto Valenciano de Oncologa (Spain), the Hospital Vall dHebron (Spain), the Hospital Sant Joan de Du (Spain), the Hospital Regional de Bata (Equatorial Guinea), the Desarrollo 2000 en frica NGO (Equatorial Guinea), the Hospital Regional de Trujillo (Peru), the Instituto Nacional de Cancerologa (Mexico), the St. John of God Hospital (Sierra Leone), CMF International, and the College of Health Sciences of the University of Nairobi in cooperation with the Kenyatta National Hospital (Kenya). The 30-month initiative, coordinated by Son Dureta, seeks to provide Web-based diagnostic and/or therapeutic support for complex medical cases requiring specialized opinions in different health areas (initially adults and pediatrics Oncology as well as Infectious Diseases). The communication among doctors and the sharing of medical cases will be performed by using a cost-efficient Web 2.0 portal that will facilitate the exchange of medical images, videos and reports. Strategic objectives of the project include the facilitation of communication and medical knowledge exchange to develop diagnostic, therapeutic and technological support actions within distinct healthcare settings, the encouragement of human resource, technology, and infrastructure investment policies, the implementation of multinational online Continuing Medical Education (CME) programs, the creation of clinical research groups, and the evaluation of an inexpensive Web platform for clinical case sharing.
Liang Y.,University of Texas Health Science Center at San Antonio |
Liang Y.,University of Texas Health Science Center at Houston |
Ketchum N.S.,University of Texas Health Science Center at San Antonio |
Louden C.,University of Texas Health Science Center at San Antonio |
And 3 more authors.
Urologia Internationalis | Year: 2012
Objectives: To perform the first validation study of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (finPCPTRC) in a contemporary referral population in Mexico. Methods: 837 patients referred to the Instituto Nacional de Cancerologa, Mexico City, Mexico, between 2005 and 2009 were used to validate the finPCPTRC by examining various measures of discrimination and calibration. Net benefit curve analysis was used to gain insight into the use of the finPCPTRC for clinical decisions. Results: Prostate cancer (PCa) incidence (72.8%) was high in this Mexican referral cohort and 45.7% of men who were diagnosed with PCa had high-grade lesions (HGPCa, Gleason score >6). 1.3% of the patients were taking finasteride. The finPCPTRC was a superior diagnostic tool compared to prostate-specific antigen alone when discriminating patients with PCa from those without PCa (AUC = 0.784 vs. AUC = 0.687, p < 0.001) and when discriminating patients with HGPCa from those without HGPCa (AUC = 0.768 vs. AUC = 0.739, p < 0.001). The finPCPTRC underestimated the risk of PCa but overestimated the risk of HGPCa (both p < 0.001). Compared with other strategies to opt for biopsy, the net benefit would be larger with utilization of the finPCPTRC for patients accepting higher risks of HGPCa. Conclusions: Rates of biopsy-detectable PCa and HGPCa were high and 1.3% of this referral cohort in Mexico was taking finasteride. The risks of PCa or HGPCa calculated by the finPCPTRC were not well calibrated for this referral Mexican population and new clinical diagnostic tools are needed. Copyright © 2012 S. Karger AG, Basel.