scholarly journals Molecular Profiling of Endometrial Cancer: An Exploratory Study in Aotearoa, New Zealand

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5641
Author(s):  
Claire E. Henry ◽  
Khoi Phan ◽  
Elena J. Orsman ◽  
Diane Kenwright ◽  
Michelle C. Thunders ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
New Zealand ◽  
Molecular Profiling ◽  
Molecular Profile ◽  
Targeted Next Generation Sequencing ◽  
Aotearoa New Zealand ◽  
Next Generation Sequencing Ngs ◽  
Ctnnb1 Mutation ◽  
Generation Sequencing ◽  
L1cam Expression

Background: Aotearoa, New Zealand, has one of the fastest-rising rates of endometrial cancer (EC) worldwide, increasing particularly in younger Māori and Pasifika women. There is a move towards using molecular profiling to direct treatment for each EC subtype. Aim: This study aimed to explore the molecular profiling of primary EC tissue in Aotearoa. Methods: We used the PORTEC guidelines for the molecular subtyping of 90 patients’ samples into four categories: POLE-mutated, p53 abnormal, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP). The CTNNB1 mutation and L1CAM expression were also included in the analysis. POLE and CTNNB1 mutations were analysed using targeted next-generation sequencing (NGS). Novel mutations were assessed using VarSome. MMRd, L1CAM and p53 abnormalities were analysed using immunohistochemistry. Results: In total, 15 samples were MMRd, 9 were p53 abnormal, 8 were POLE-mutated and the rest (56) were NSMP. Eleven samples had exon 3 CTNNB1 mutations and eleven novel POLE mutations were described. Conclusion: Surrogate markers for POLE mutations should be investigated. The validation of POLE variants and CTNNB1 mutations as part of an Aotearoa-based molecular panel is warranted.

scholarly journals The ICR96 exon CNV validation series: a resource for orthogonal assessment of exon CNV calling in NGS data

2017 ◽  
Vol 2 ◽  
pp. 35 ◽  
Author(s):  
Shazia Mahamdallie ◽  
Elise Ruark ◽  
Shawn Yost ◽  
Emma Ramsay ◽  
Imran Uddin ◽  
...  
Keyword(s):  
Sequencing Data ◽  
Targeted Next Generation Sequencing ◽  
Negative Results ◽  
Targeted Ngs ◽  
Predisposition Genes ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Validation Series ◽  
Generation Sequencing ◽  
Dependent Probe

Detection of deletions and duplications of whole exons (exon CNVs) is a key requirement of genetic testing. Accurate detection of this variant type has proved very challenging in targeted next-generation sequencing (NGS) data, particularly if only a single exon is involved. Many different NGS exon CNV calling methods have been developed over the last five years. Such methods are usually evaluated using simulated and/or in-house data due to a lack of publicly-available datasets with orthogonally generated results. This hinders tool comparisons, transparency and reproducibility. To provide a community resource for assessment of exon CNV calling methods in targeted NGS data, we here present the ICR96 exon CNV validation series. The dataset includes high-quality sequencing data from a targeted NGS assay (the TruSight Cancer Panel) together with Multiplex Ligation-dependent Probe Amplification (MLPA) results for 96 independent samples. 66 samples contain at least one validated exon CNV and 30 samples have validated negative results for exon CNVs in 26 genes. The dataset includes 46 exon CNVs in BRCA1, BRCA2, TP53, MLH1, MSH2, MSH6, PMS2, EPCAM or PTEN, giving excellent representation of the cancer predisposition genes most frequently tested in clinical practice. Moreover, the validated exon CNVs include 25 single exon CNVs, the most difficult type of exon CNV to detect. The FASTQ files for the ICR96 exon CNV validation series can be accessed through the European-Genome phenome Archive (EGA) under the accession number EGAS00001002428.

scholarly journals Targeted Next Generation Sequencing (NGS) to Diagnose Hereditary Hemolytic Anemias

2020 ◽  
Author(s):  
Rishab Bharadwaj ◽  
Thulasi Raman ◽  
Ravikumar Thangadorai ◽  
Deenadayalan Munirathnam
Keyword(s):  
Next Generation Sequencing ◽  
Gene Sequencing ◽  
Accurate Diagnosis ◽  
Next Generation ◽  
Diagnostic Challenge ◽  
Targeted Next Generation Sequencing ◽  
Appropriate Treatment ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Hereditary hemolytic anemias present a unique diagnostic challenge due to their wide phenotypic and genotypic spectrum. Accurate diagnosis is essential to ensure appropriate treatment. We report two cases, which presented as hemolytic anemias, but initial workup was inconclusive and they were finally diagnosed with the help of Next Generation Sequencing (Dehydrated Hereditary Stomatocytosis and Kӧln Hemoglobinopathy). The introduction of gene sequencing to aid diagnosis of these disorders is a revolutionary step forward and should be incorporated earlier in the workup of such patients.

scholarly journals Molecular Profiling of Malignant Pleural Effusions with Next Generation Sequencing (NGS): Evidence that Supports Its Role in Cancer Management

2020 ◽  
Vol 10 (4) ◽  
pp. 206
Author(s):  
Georgia Ι. Grigoriadou ◽  
Stepan M. Esagian ◽  
Han Suk Ryu ◽  
Ilias P. Nikas
Keyword(s):  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Liquid Biopsy ◽  
Molecular Profiling ◽  
Pleural Effusions ◽  
Advanced Cancer Patients ◽  
Cancer Management ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Malignant pleural effusions (MPEs) often develop in advanced cancer patients and confer significant morbidity and mortality. In this review, we evaluated whether molecular profiling of MPEs with next generation sequencing (NGS) could have a role in cancer management, focusing on lung cancer. We reviewed and compared the diagnostic performance of pleural fluid liquid biopsy with other types of samples. When applied in MPEs, NGS may have comparable performance with corresponding tissue biopsies, yield higher DNA amount, and detect more genetic aberrations than blood-derived liquid biopsies. NGS in MPEs may also be preferable to plasma liquid biopsy in advanced cancer patients with a MPE and a paucicellular or difficult to obtain tissue/fine-needle aspiration biopsy. Of interest, post-centrifuge supernatant NGS may exhibit superior results compared to cell pellet, cell block or other materials. NGS in MPEs can also guide clinicians in tailoring established therapies and identifying therapy resistance. Evidence is still premature regarding the role of NGS in MPEs from patients with cancers other than lung. We concluded that MPE processing could provide useful prognostic and theranostic information, besides its diagnostic role.

scholarly journals Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1290
Author(s):  
Jennifer S. Winn ◽  
Zachary Hasse ◽  
Michael Slifker ◽  
Jianming Pei ◽  
Sebastian M. Arisi-Fernandez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Triple Negative ◽  
Genetic Profile ◽  
Cell Free Dna ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Free Dna ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in TP53 (47.3%), PMS2 (26.3%), MRE11 (26.3%), RB1 (10.5%), BRCA1 (10.5%), PTEN (10.5%) and AR (10.5%); other affected genes included PMS1, KMT2C, BRCA2, PALB2, MUTYH, MEN1, MSH2, CHEK2, NCOR1, PIK3CA, ESR1 and MAP2K4. In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AFtissue ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.

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