RESUMO
Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low susceptibility risk loci have been identified for both sporadic and familial cases. Therefore, we tried to identify new susceptibility genes responsible for familial testicular cancer that may contribute to increasing our knowledge about the genetic basis of the disease. Nineteen Spanish families with at least two affected individuals with TGCT were selected. WES was performed on those individuals using an Illumina Hiseq2000 sequencing platform. Data were analyzed under a monogenic and polygenic model of inheritance, and candidate variants were evaluated in a case-control association study performed on 391 Spanish sporadic cases and 1,170 healthy Spanish controls. Results were replicated in a second series consisting of 101 TGCTs from the Cancer Genome Atlas (TGCA) and 27,000 controls from the Exome Aggregation Consortium (ExAC) database. Logistic regression was carried out to analyze the association strength (risk) of candidate variants obtained among cases and controls in different populations. Despite the sample size, we detected a significant earlier age of onset in familial TGCT (28y) than sporadic cases (33y), using a Mann-Whitney U test. We identified significant variants in the comparative study of TGCT cases (391) versus controls (almost 1,170), and three of them [PLEC (OR = 6.28, p = 6.42 × 10-23 ) (p.Arg2016Trp), EXO5 (OR = 3.37, p = 4.82 × 10-09 ) (p.Arg344AlafsTer10) and DNAH7 (OR = 1.64, p = 0.048)] were replicated as potential candidates that may contribute to explaining the genetic basis of TGCT.
Assuntos
Dineínas do Axonema/genética , Exonucleases/genética , Predisposição Genética para Doença/genética , Plectina/genética , Neoplasias Testiculares/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Exoma/genética , Feminino , Hereditariedade/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , Fatores de Risco , Sequenciamento do Exoma/métodos , Adulto JovemRESUMO
Carcinoids of the ampulla of Vater are infrequent tumors of which a quarter of cases have been detected in patients with type I neurofibromatosis. This hereditary disease is also associated with gastrointestinal stromal tumors (GIST). However, the coincidence of these three entities together have only been formerly detected in five cases. A 53 year-old female patient, diagnosed with type I neurofibromatosis, with a malignant carcinoid of ampulla of Vater and multiple gastrointestinal stromal tumors in the duodenum and jejunum, was treated with total pancreatectomy and the excision of her intestinal tumors. Five-years on, a follow-up showed the patient to be well, and free from tumor recurrence. The coexistence of an ampullary carcinoid tumor, GIST and neurofibramatosis is very rare. Radical curative surgical resection is a good treatment option, but the optimal management of this is not yet well established.
Assuntos
Ampola Hepatopancreática/patologia , Tumores do Estroma Gastrointestinal/patologia , Neurofibromatoses/patologia , Neoplasias Pancreáticas/patologia , Ampola Hepatopancreática/cirurgia , Feminino , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Pessoa de Meia-Idade , Neurofibromatoses/cirurgia , Neoplasias Pancreáticas/cirurgiaRESUMO
Vesical clear cell adenocarcinoma is an uncommon tumour. The description of nearly all published cases focuses on histological issues, providing few clinical particulars and limited followup. The treatment choice is resection. No publications have been found regarding systemic treatments for advanced disease. We present a case of metastatic clear cell adenocarcinoma of the bladder treated with chemotherapy.