The bigger the better? Evaluation of the value of large multi-gene panels in Portuguese cardiomyopathy genetic testing

Introduction: Genetic testing of cardiomyopathies went through major changes in the last few years, from sequential Sanger sequencing of the most likely gene candidates, to multigene panels by NGS, with an ever increasing number of genes analyzed.info:eu-repo/semantics/publishedVersio

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations. In probands negative for CDH1 mutations, we screened genes involved in hereditary cancer syndromes in which gastric cancer may be one of the component tumours, namely p53 (Li-Fraumeni Syndrome) and hMLH1 and hMSH2 (HNPCC). We also screened in these patients for mutations in Caspase-10, a gene inactivated in sporadic gastric cancer, and SMAD4, a gene whose inactivation in mice is associated with signet-ring cell carcinoma of the stomach. One of the families fulfilling the HDGC criteria harboured a CDH1 germline mutation, and one of the families with incomplete criteria harboured a p53 germline mutation. No mutations were identified in hMLH1 and hMSH2, and only sequence variants were found in SMAD4 and Caspase-10. The present work reports for the first time CDH1 germline mutations in Portuguese gastric cancer families, and highlights the need for p53 mutation screening in families lacking CDH1 germline mutations, in a country with one of the highest incidences of gastric cancer in the world. No evidence was found for a role of germline mutations in SMAD4 and Caspase-10 in families lacking CDH1 mutations.http://www.sciencedirect.com/science/article/B6T68-4CP0YVH-5/1/0b2a789fc5dbe341d589aa4cee90b9e

Mc4r mutations in a sample of morbid obese Portuguese patients.

[resumo][abstract

Especificidade do teste de provocação na Síndrome de Brugada: a queda de um mito

O rastreio de familiares de doentes com Síndrome de Brugada (SB) com ECG basal não diagnóstico deve incluir o teste de provocação farmacológica e se for induzido o padrão de repolarização do tipo 1 o diagnóstico é concluído sem mais corroboração. Este teste é realizado com o pressuposto de não existirem falsos positivos mas a verdadeira especificidade é desconhecida

Pathogenesis of testicular germ cell tumors a cytogenetical and pathological study

testicular germ cell tumors of adults can be divided both clinically and morphologically in two distinct entities, seminoma and nonseminoma.... Zie: Summary

E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients

Approximately 30% of all hereditary diffuse gastric cancer (HDGC) families carry CDH1 germline mutations. The other two thirds remain genetically unexplained and are probably caused by alterations in other genes. Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations. In probands negative for CDH1 mutations, we screened genes involved in hereditary cancer syndromes in which gastric cancer may be one of the component tumours, namely p53 (Li-Fraumeni Syndrome) and hMLH1 and hMSH2 (HNPCC). We also screened in these patients for mutations in Caspase-10, a gene inactivated in sporadic gastric cancer, and SMAD4, a gene whose inactivation in mice is associated with signet-ring cell carcinoma of the stomach. One of the families fulfilling the HDGC criteria harboured a CDH1 germline mutation, and one of the families with incomplete criteria harboured a p53 germline mutation. No mutations were identified in hMLH1 and hMSH2, and only sequence variants were found in SMAD4 and Caspase-10. The present work reports for the first time CDH1 germline mutations in Portuguese gastric cancer families, and highlights the need for p53 mutation screening in families lacking CDH1 germline mutations, in a country with one of the highest incidences of gastric cancer in the world. No evidence was found for a role of germline mutations in SMAD4 and Caspase-10 in families lacking CDH1 mutations.http://www.sciencedirect.com/science/article/B6T68-4CP0YVH-5/1/0b2a789fc5dbe341d589aa4cee90b9e

No significant role for beta tubulin mutations and mismatch repair defects in ovarian cancer resistance to paclitaxel/cisplatin

Abstract Background The mechanisms of chemoresistance in ovarian cancer patients remain largely to be elucidated. Paclitaxel/cisplatin combination is the standard chemotherapeutic treatment for this disease, although some patients do not respond to therapy. Our goals were to investigate whether TUBB mutations and mismatch repair defects underlie paclitaxel and cisplatin resistance. Methods Thirty-four patients with primary ovarian carcinomas (26 serous and eight clear cell carcinomas) treated with paclitaxel/cisplatin were analysed. TUBB exon 4 was analysed by nested PCR after a first round PCR using intronic primers. Microsatellite analysis was performed with the quasimonomorphic markers BAT 26 and BAT 34. Results Twenty-two of the 34 ovarian cancers (64.7%) presented residual tumour after surgery, seven of which (7/22; 31.8%) were shown to be chemoresistant (five serous and two clear cell tumours). Sequence analysis did not find any mutation in TUBB exon 4. Microsatellite instability was not detected in any of the ovarian carcinomas. Conclusion We conclude that TUBB exon 4 mutations and mismatch repair defects do not play a significant role in paclitaxel/cisplatin resistance.</p

Cytogenetic study of a combined germ cell tumor of the testis

The cytogenetic findings in both components of a combined germ cell tumor of the testis are described. The only structural chromosomal abnormality in common was an i(12p)

Karyotyping and DNA flow cytometry of an orchidoblastoma

The first karyotype of an orchidoblastoma is described. The most striking finding is the absence of the i(12p) marker chromosome, considered specific for testicular germ cell tumors of adults. Differences between infantile and adult testicular germ cell tumors are discussed, as are features that infantile testicular germ cell tumors have in common with extragonadal germ cell tumors