RESUMO
BACKGROUND: The success of multisite collaborative research relies on effective data collection, harmonization, and aggregation strategies. Data Coordination Centers (DCC) serve to facilitate the implementation of these strategies. The utility of a DCC can be particularly relevant for research on rare diseases where collaboration from multiple sites to amass large aggregate datasets is essential. However, approaches to building a DCC have been scarcely documented. METHODS: The Li-Fraumeni Exploration (LiFE) Consortium's DCC was created using multiple open source packages, including LAM/G Application (Linux, Apache, MySQL, Grails), Extraction-Transformation-Loading (ETL) Pentaho Data Integration Tool, and the Saiku-Mondrian client. This document serves as a resource for building a rare disease DCC for multi-institutional collaborative research. RESULTS: The primary scientific and technological objective to create an online central repository into which data from all participating sites could be deposited, harmonized, aggregated, disseminated, and analyzed was completed. The cohort now include 2,193 participants from six contributing sites, including 1,354 individuals from families with a pathogenic or likely variant in TP53. Data on cancer diagnoses are also available. Challenges and lessons learned are summarized. CONCLUSIONS: The methods leveraged mitigate challenges associated with successfully developing a DCC's technical infrastructure, data harmonization efforts, communications, and software development and applications. IMPACT: These methods can serve as a framework in establishing other collaborative research efforts. Data from the consortium will serve as a great resource for collaborative research to improve knowledge on, and the ability to care for, individuals and families with Li-Fraumeni syndrome.
Assuntos
Troca de Informação em Saúde , Cooperação Internacional , Síndrome de Li-Fraumeni/epidemiologia , Doenças Raras/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Coleta de Dados/métodos , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Carga Global da Doença , Humanos , Lactente , Recém-Nascido , Internet , Síndrome de Li-Fraumeni/genética , Masculino , Pessoa de Meia-Idade , Doenças Raras/genética , Tamanho da Amostra , Proteína Supressora de Tumor p53/genética , Adulto JovemRESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.
Assuntos
Transtornos de Deglutição/genética , Tumores do Estroma Gastrointestinal/genética , Mutação em Linhagem Germinativa/genética , Melanose/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Adulto , Criança , Transtornos de Deglutição/diagnóstico , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Imuno-Histoquímica , Masculino , Melanose/diagnóstico , Pessoa de Meia-Idade , LinhagemRESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.
Assuntos
Melanose/genética , Mutação em Linhagem Germinativa/genética , Proteínas Proto-Oncogênicas c-kit/genética , Transtornos de Deglutição/genética , Tumores do Estroma Gastrointestinal/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Imuno-Histoquímica , Linhagem , Masculino , Melanose/diagnóstico , Pessoa de Meia-Idade , Transtornos de Deglutição/diagnóstico , Tumores do Estroma Gastrointestinal/diagnósticoRESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T > C (p.559V > A) substitution in exon 11. Treatment with imatinib is furnishing positive results.
