scholarly journals Somatic BRCA Mutation in Cholangiocarcinoma Patient Utilized to Individualize an HBOC Syndrome

2019 ◽  
Author(s):  
Angelo Paradiso ◽  
Margherita Patruno ◽  
Maria Digennaro ◽  
Stefania Tommasi ◽  
Brunella Pilato ◽  
...  
Keyword(s):  
Absolute Risk ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Pathogenic Variant ◽  
Cancer Syndrome ◽  
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Brca2 Gene Mutation ◽  
First Time ◽  
Formalin Fixed

BRCA-associated hereditary breast and ovarian cancer syndrome (HBOC) implies increased absolute risk also for other malignancies such as cholangiocarcinoma (CCA). However, even if somatic mutations in CCA have been reported, there are no data on its utilization as predisposing genetic factor in a family. For the first time, we utilized CCA somatic BRCA mutation to individualize a family with HBOC. A 47-year-old woman (daughter of a patient died for CCA) accessed to our Genetic Councelling to evaluate her personal cancer risk. We performed a somatic BRCA1/2 NGS analysis on DNA extracted from formalin-fixed, paraffin-embedded CCA-tissue of her mother. After demonstration of pathogenic variant c.6468_6469delTC in BRCA2 gene mutation, the same germline pathogenic variant was found in DNA blood of one of two daugthers. So far, CCA tissue can be utilized, in addition to patient’s selection to specific therapeutic strategies, also to individualize families belonging to HBOC syndrome.

Paraffin-based molecular diagnosis of lung cancer reproduces morphologic and molecular subtypes of lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7579-7579
Author(s):  
D. N. Hayes ◽  
J. Schallheim ◽  
P. Roberts ◽  
C. Lee ◽  
L. Thorne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Clinical Practice ◽  
Molecular Subtypes ◽  
Pcr Assay ◽  
Lung Cancer Patients ◽  
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First Time ◽  
Formalin Fixed

7579 Background: Molecular profiling of lung cancer by gene expression analyses has documented potential to guide therapy. However, quality ‘fresh’ tissue for RNA analyses is generally unavailable in clinical practice. We introduce a (q)RT-PCR assay and analytic method for profiling lung cancers from clinically obtained formalin-fixed paraffin-embedded tissues. Methods: Approximately 1,000 DNA microarrays were analyzed to select genes distinguishing the major histological variants (adenocarcinoma, small cell carcinoma, etc) and previously described molecular subtypes of lung cancer. Based on gene expression, a classifier of 62 genes was constructed to assign each sample to its morphologic tumor type, as well as to risk stratify by molecular subtypes. A real-time qRT-PCR assay was developed to evaluate the expression of the 62 genes from paraffin-embedded samples. This assay was used to profile RNA extracted from a cohort of surgically treated lung cancer patients. Samples were procured as fresh frozen and formalin-fixed, paraffin-embedded and were archived between 1–15 years. Results: Fifty-eight of 62 genes passed performance criteria and were used for analyses. Normalized gene expression was used for sample classification. The cohort contained a broad spectrum of tumors in proportions consistent with clinical practice. Gene amplification was successful in 139 of 142 (98%) lung cancer samples. Matched frozen-paraffin and replicate paraffin samples had mean correlations of approximately 80%. Linear discriminant analysis of gene expression data agreed with morphologic classification by light microscopy in >99% of cases. More importantly, the method successfully re-identified molecular subtypes of lung cancer for the first time through the use of a paraffin-based assay. Clinical outcomes previously associated with molecular tumor subtypes, including differential survival and metastatic patterns, were again seen in our cohort. Conclusions: We describe for the first time a clinically meaningful and robust molecular diagnosis of a clinical cohort of lung cancer patients which is complementary to morphologic cancer diagnosis. This assay is easily implemented using specimens routinely collected in current patient care. No significant financial relationships to disclose.

Proteome Analysis of Formalin-Fixed Paraffin-Embedded Tissues from a Primary Gastric Melanoma and its Meningeal Metastasis: A Case Report

2014 ◽  
Vol 14 (3) ◽  
pp. 382-387 ◽  
Author(s):  
Juliana Fischer ◽  
Nathalie Canedo ◽  
Katia Goncalves ◽  
Leila Chimelli ◽  
Monique Franca ◽  
...  
Keyword(s):  
Case Report ◽  
Proteome Analysis ◽  
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scholarly journals Identification and Validation of New Cancer Stem Cell-Related Genes and Their Regulatory microRNAs in Colorectal Cancerogenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 179
Author(s):  
Kristian Urh ◽  
Margareta Žlajpah ◽  
Nina Zidar ◽  
Emanuela Boštjančič
Keyword(s):  
Experimental Validation ◽  
Target Gene ◽  
Bioinformatics Analysis ◽  
Early Carcinoma ◽  
Significant Progress ◽  
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Node Metastases ◽  
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Made In

Significant progress has been made in the last decade in our understanding of the pathogenetic mechanisms of colorectal cancer (CRC). Cancer stem cells (CSC) have gained much attention and are now believed to play a crucial role in the pathogenesis of various cancers, including CRC. In the current study, we validated gene expression of four genes related to CSC, L1TD1, SLITRK6, ST6GALNAC1 and TCEA3, identified in a previous bioinformatics analysis. Using bioinformatics, potential miRNA-target gene correlations were prioritized. In total, 70 formalin-fixed paraffin-embedded biopsy samples from 47 patients with adenoma, adenoma with early carcinoma and CRC without and with lymph node metastases were included. The expression of selected genes and microRNAs (miRNAs) was evaluated using quantitative PCR. Differential expression of all investigated genes and four of six prioritized miRNAs (hsa-miR-199a-3p, hsa-miR-335-5p, hsa-miR-425-5p, hsa-miR-1225-3p, hsa-miR-1233-3p and hsa-miR-1303) was found in at least one group of CRC cancerogenesis. L1TD1, SLITRK6, miR-1233-3p and miR-1225-3p were correlated to the level of malignancy. A negative correlation between miR-199a-3p and its predicted target SLITRK6 was observed, showing potential for further experimental validation in CRC. Our results provide further evidence that CSC-related genes and their regulatory miRNAs are involved in CRC development and progression and suggest that some them, particularly miR-199a-3p and its SLITRK6 target gene, are promising for further validation in CRC.

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