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Carraro D.M.,National Institute of Science and Technology in Oncogenomics INCITO | Andrade V.P.,Ac Camargo Cancer Center
Bioscience Reports | Year: 2014

The spread of mammographic screening programmes around the world, including in developing countries, has substantially contributed to the diagnosis of small non-palpable lesions, which has increased the detection rate of DCIS (ductal carcinoma in situ). DCIS is heterogeneous in several ways, such as its clinical presentation, morphology and genomic profile. Excellent outcomes have been reported; however, many questions remain unanswered. For example, which patients groups are overtreated and could instead benefit from minimal intervention and which patient groups require a more traditional multidisciplinary approach. The development of a comprehensive integrated analysis that includes the radiological, morphological and genetic aspects of DCIS is necessary to answer these questions. This review focuses on discussing the significant findings about the morphological and molecular features of DCIS and its progression that have helped to uncover the biological and genetic heterogeneity of this disease. The knowledge gained in recent years might allow the development of tailored clinical management for women with DCIS in the future. © 2014 The Author(s). Source


Olivieri E.H.R.,Camargo Cancer Center | De Andrade Franco L.,International Cancer Center | Pereira R.G.,International Cancer Center | Carvalho Mota L.D.,Camargo Cancer Center | And 4 more authors.
Biopreservation and Biobanking | Year: 2014

A critical issue in defining protocols for biobanking practices is the preservation of total RNA for assessing the whole transcriptome and ensuring that it can be utilized in clinically oriented studies. Storage conditions, such as temperature and the length of time that tissues and purified RNA stay frozen, may directly impact RNA preservation. In this study, we evaluated a) the quality of RNA (as measured by RNA Integrity Number) purified from head and neck tumor tissues stored at -140 C for distinct time intervals of up to 7 years, and b) the quality of their respective RNAs stored for 4 years at -80 C when diluted at either 250 ng/μL or 25 ng/μL, with repeated freezing and thawing. Additionally, we generated a profile of the RNA collection of human tumors from different body sites stored at the AC Camargo Biobank. Our results showed no significant change in RIN values according to length of storage at -140 C. With respect to RNA aliquots stored at -80 C, RNA integrity at 250 ng/μL was preserved, while statistically significant degradation was observed at 25 ng/μL after only 8 months of storage. The RNA collection from most of the human tumors stored at the AC Camargo Biobank exhibited high quality, with average RIN around seven. However, ovary and stomach samples had the greatest RNA degradation. Taken together, the results show that both the temperature of preservation and the concentration of RNA should be strictly controlled by the biobank staff involved in macromolecule purification. Moreover, the RNAs from our biobank can be useful for the most demanding methods of gene expression analysis by virtue of adherence to optimal standard operating procedures for both tissue and macromolecule laboratories. © Mary Ann Liebert, Inc. Source


Carraro D.M.,Laboratory of Genomics and Molecular Biology | Carraro D.M.,National Institute of Science and Technology in Oncogenomics INCITO | Koike Folgueira M.A.A.,University of Sao Paulo | Garcia Lisboa B.C.,Laboratory of Genomics and Molecular Biology | And 16 more authors.
PLoS ONE | Year: 2013

Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) [7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients. © 2013 Carraro et al. Source


Torrezan G.T.,Laboratory of Genomics and Molecular Biology | Da Silva F.C.C.,Laboratory of Genomics and Molecular Biology | Santos E.M.M.,National Institute of Science and Technology in Oncogenomics INCITO | Krepischi A.C.V.,National Institute of Science and Technology in Oncogenomics INCITO | And 6 more authors.
Orphanet Journal of Rare Diseases | Year: 2013

Background: Patients with multiple colorectal adenomas are currently screened for germline mutations in two genes, APC and MUTYH. APC-mutated patients present classic or attenuated familial adenomatous polyposis (FAP/AFAP), while patients carrying biallelic MUTYH mutations exhibit MUTYH-associated polyposis (MAP). The spectrum of mutations as well as the genotype-phenotype correlations in polyposis syndromes present clinical impact and can be population specific, making important to obtain genetic and clinical data from different populations. Methods. DNA sequencing of the complete coding region of the APC and MUTYH genes was performed in 23 unrelated Brazilian polyposis patients. In addition, mutation-negative patients were screened for large genomic rearrangements by multiplex ligation-dependent probe amplification, array-comparative genomic hybridization, and duplex quantitative PCR. Biallelic MUTYH mutations were confirmed by allele-specific PCR. Clinical data of the index cases and their affected relatives were used to assess genotype-phenotype correlations. Results: Pathogenic mutations were identified in 20 of the 23 probands (87%): 14 in the APC gene and six in the MUTYH gene; six of them (30%) were described for the first time in this series. Genotype-phenotype correlations revealed divergent results compared with those described in other studies, particularly regarding the extent of polyposis and the occurrence of desmoid tumors in families with mutations before codon 1444 (6/8 families with desmoid). Conclusions: This first comprehensive investigation of the APC and MUTYH mutation spectrum in Brazilian polyposis patients showed a high detection rate and identified novel pathogenic mutations. Notably, a significant number of APC-positive families were not consistent with the predicted genotype-phenotype correlations from other populations. © 2013 Torrezan et al.; licensee BioMed Central Ltd. Source


Jardim J.F.,University of Campinas | Francisco A.L.N.,National Institute of Science and Technology in Oncogenomics INCITO | Gondak R.,Federal University of Santa Catarina | Damascena A.,International Center for Cancer Research | And 2 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2015

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. © 2014 International Association of Oral and Maxillofacial Surgeons. Source

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