scholarly journals PIK3CA and p53 Mutations by Next Generation Sequencing in Lymphoepithelioma-Like Carcinoma of the Endometrium

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Lucie Bienfait ◽  
Nicky D’Haene ◽  
Xavier Catteau ◽  
Jean-Christophe Noël
Keyword(s):  
Next Generation Sequencing ◽  
T Lymphocytes ◽  
Endometrial Carcinoma ◽  
Cytotoxic T Lymphocytes ◽  
Plasma Cells ◽  
P53 Gene ◽  
P53 Mutations ◽  
Next Generation ◽  
Molecular Features ◽  
Generation Sequencing

Lymphoepithelioma-like carcinoma of the endometrium is a very rare variant of endometrial carcinoma characterized by syncytial nests of pleomorphic epithelial cells and heavy infiltration of the stroma by lymphocytes (in particular CD8 cytotoxic T-lymphocytes) and plasma cells. Until now, only five cases have been characterized in this location. This report describes the clinicopathological and the molecular features of this unusual tumor. In particular, using the next generation sequencing (NGS) technique, we have demonstrated that this tumor could be associated with PIK3CA and p53 gene mutations. These data have not been reported to date and suggest that lymphoepithelioma-like carcinoma of the endometrium shares common molecular features with high grade endometrioid and serous-like endometrial carcinoma which are associated with poor outcome. Nevertheless, in endometrial lymphoepithelioma-like carcinoma, the alterations on cell cycle, apoptosis, and/or senescence secondary to p53 mutations could potentially be counterbalanced by the antitumoral response induced by CD8 cytotoxic T-lymphocytes numerous in these tumors.

scholarly journals Next-Generation Sequencing Reveals High Uncommon EGFR Mutations and Tumour Mutation Burden in a Subgroup of Lung Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Guo ◽  
Gaofeng Li ◽  
Yinqiang Liu ◽  
Heng Li ◽  
Qi Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Kinase Inhibitors ◽  
The Cancer Genome Atlas ◽  
Egfr Mutations ◽  
Next Generation ◽  
Molecular Features ◽  
Mutation Burden ◽  
Incidence And Mortality ◽  
Generation Sequencing

Xuanwei County in Southwest China shows the highest incidence and mortality rate of lung cancer in China. Although studies have reported distinct clinical characteristics of patients from Xuanwei, the molecular features of these patients with non-small cell lung cancer (NSCLC) remain unclear. Here, we comprehensively characterised such cases using next-generation sequencing (NGS). Formalin-fixed, paraffin-embedded tumour samples from 146 patients from Xuanwei with NSCLC were collected for an NGS-based target panel assay; their features were compared with those of reference Chinese and The Cancer Genome Atlas (TCGA) cohorts. Uncommon EGFR mutations, defined as mutations other than L858R, exon 19del, exon 20ins, and T790M, were the predominant type of EGFR mutations in the Xuanwei cohort. Patients harbouring uncommon EGFR mutations were more likely to have a family history of cancer (p = 0.048). A higher frequency of KRAS mutations and lower frequency of rearrangement alterations were observed in the Xuanwei cohort (p < 0.001). Patients from Xuanwei showed a significantly higher tumour mutation burden than the reference Chinese and TCGA cohorts (p < 0.001). Our data indicates that patients from Xuanwei with NSCLC harbouring G719X/S768I co-mutations may benefit from treatment with EGFR-tyrosine kinase inhibitors. Our comprehensive molecular profiling revealed unique genomic features of patients from Xuanwei with NSCLC, highlighting the potential for improvement in targeted therapy and immunotherapy.

scholarly journals Immunohistochemistry and Next-generation Sequencing Are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Linyuan Wang ◽  
Anna Piskorz ◽  
Tjalling Bosse ◽  
Mercedes Jimenez-Linan ◽  
Brian Rous ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Endometrial Carcinoma ◽  
Next Generation ◽  
Generation Sequencing

Identifying large indels in targeted next generation sequencing assays for myeloid neoplasms: a cautionary tale of the ZRSR1 pseudogene

2017 ◽  
Vol 70 (12) ◽  
pp. 1069-1073 ◽  
Author(s):  
Isaac KS Ng ◽  
Christopher Ng ◽  
Jia Jin Low ◽  
Lily Chiu ◽  
Elaine Seah ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Diagnostics ◽  
Great Promise ◽  
Next Generation ◽  
Bioinformatics Pipeline ◽  
Targeted Next Generation Sequencing ◽  
Molecular Features ◽  
Myeloid Neoplasms ◽  
Large Indels ◽  
Generation Sequencing

Targeted next generation sequencing platforms have been increasingly utilised for identification of novel mutations in myeloid neoplasms, such as acute myeloid leukaemia (AML), and hold great promise for use in routine clinical diagnostics. In this study, we evaluated the utility of an open source variant caller in detecting large indels in a targeted sequencing of AML samples. While we found that this bioinformatics pipeline has the potential to accurately capture large indels (>20 bp) in patient samples, we highlighted the pitfall of a confounding ZRSR1 pseudogene that led to an erroneous ZRSR2 variant call. We further discuss possible clinical implications of the ZRSR1 pseudogene in myeloid neoplasms based on its molecular features. Knowledge of the confounding ZRSR1 pseudogene in ZRSR2 sequencing assays could be particularly important in AML diagnostics because the detection of ZRSR2 in AML patients is highly specific for an s-AML diagnosis.

Clinical significance of next-generation sequencing in Chinese patients with relapsed/refractory Wilm’s tumor.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22003-e22003
Author(s):  
Juan Wang ◽  
Fei-fei Sun ◽  
Wanming Hu ◽  
Lian Zhang ◽  
Qing WANG ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Wilms Tumor ◽  
Copy Number Variations ◽  
Chinese Patients ◽  
Driver Mutations ◽  
Cancer Center ◽  
Large Sample Size ◽  
Next Generation ◽  
Molecular Features ◽  
Generation Sequencing

e22003 Background: Medical advances have been greatly improved in the survival rate for Wilms’ tumor, but the survival is still dismal for relapsed/refractory (R/R) patients. In the present study, we aimed to investigated the genomic profiling and the incidence of germline cancer susceptibility mutations of Chinese patients with R/R WT. Methods: From Jun 18, 2020 to Dec 22, 2020, the tumor specimens with matched blood samples obtained from R/R pediatric WT in Sun Yat-Sen University Cancer Center were performed next-generation sequencing (NGS) using a 539 cancer-related gene panel in a CAP-certified laboratory (Simcere Diagnostic Co, Ltd). Clinical information including age, gender and tumor histology were collected. Somatic and germline variations including single nucleotide variants (SNV), insertion-deletion variants (Indels), copy number variations (CNVs) and fusion, as well as tumor mutational burden (TMB)/microsatellite instability (MSI) were analyzed. IHC staining for PD-L1 expression was performed by FDA-approved VENTANA PD-L1(SP263) assay. Results: Eight patients with R/R WT were enrolled in this study, including 5 males and 3 females, with a median age of 6 years old (range, 3-14). All of the pathology was identified as favorable histology WT (FHWT). Of the specimens, 8 were from pulmonary and 1from peritoneum. We identified 152 reportable molecular aberrations, with a median of 19 (0-24). CNVs accounted for the majority of the total somatic aberrations, followed by SNVs, the percentage was 77% and 22%, respectively. Genes with either CNVs or SNVs were detected in FGFR1 (n=4), ERBB2(n=3), MYCN(n=4), MET(n=2), CDK4/6(n=2), TP53(n=2), CTNNB1(n=2), MYC(n=2), NF1(n=2), MDM4(n=2), CHEK2(n=1), FBXW7(n=1), EGFR(n=1). Notable cancer driver mutations were also characterized, such as the amplifications of ERBB2/MET/EGFR/FGFR1, and the point variations of CHEK2/FBXW7/NF1. Besides, a novel ASB12 intergenic region- AMER1 fusion was identified. Both of the patients available for PD-L1 evaluation showed negative PD-L1 expression on tumor cells. The median TMB was 1.47 (range, 0-7.8). All patients were microsatellite stabilization (MSS). A 4-year-old patient suffering peritoneal relapse harbored a germline pathogenic mutation in FANCA (c.1777-1G>C, intron 19), this locus has never been reported in WT before. Conclusions: We discovered some driver genes mutations which potentially sensitive to the corresponding targeted drugs in Chinese R/R WT patients. Large sample size was needed to provide a better understanding of molecular features in R/R WT patients to achieve precision medicine.

Comprehensive next-generation sequencing to portray distinctive molecular characteristics of hypermutant lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15255-e15255
Author(s):  
Hongbin Zhang ◽  
Yuan Wang ◽  
Qiaoxia Ji ◽  
Hongmei Cai ◽  
Xiangcun Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Genetic Factors ◽  
Brca1 Gene ◽  
Driver Mutations ◽  
Molecular Characteristics ◽  
Next Generation ◽  
Molecular Features ◽  
Genetic Profiles ◽  
Generation Sequencing

e15255 Background: Tumor mutation burden (TMB) has been confirmed to predict the sensitivity to immunotherapy across multiple tumor types. Multiple genetic factors have been confirmed to increase the level of TMB, such as mutations in DNA damage repair (DDR) genes, POLE/POLD1, and high microsatellite instability (MSI). However, the extent that these factors contribute to hypermutation in lung cancer has not been fully investigated. Methods: We retrospectively reviewed the genetic profiles of 1000 lung cancer patients (pts) who underwent 1021-panel matched tumor-normal next-generation sequencing using tumor tissue samples and peripheral blood. Their TMB status were analyzed to determine the threshold of hypermutation. The clinicopathological characteristics, genetic profiles and genetic factors related to hypermutation were investigated for the pts in hypermutant cohort. Results: The threshold of hypermutation was determined as 19 muts/MB (top 5% in 1000 pts). As a result, 53 pts were included in the hypermutant cohort. A total of 1725 nonsynonymous somatic variants in 506 genes were identified. The most frequently mutated genes included TP53 (88.7%), LRP1B (71.7%), MLL2 (35.8%), EPHA5 (34.0%), and FAT1 (34.0%). KRAS was mutated in 17% pts, whereas mutations in EGFR, BRAF, ERBB2, MET were identified less commonly. MSI-high was observed in 5 cases. A germline mutation in BRCA1 gene was identified in an adenocarcinoma patient. Compared to genetic profiles of non-small cell lung cancer from TCGA database, mutations in multiple DDR genes were enriched in the hypermutant cohort (Table). No known driver mutation in POLE/POLD1 was identified. Conclusions: MSI-high and mutations in DDR genes may be associated with high level of TMB, whereas POLE/POLD1 driver mutations may not be related to hypermutant lung cancer. Hypermutant lung cancer displays distinctive molecular features that may be used as complementary indicators to screening pts sensitive to immunotherapy. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document