scholarly journals Can Discord Domain-Containing Receptor 2 Mutation Act as a Disease Modifier for PRKAR1A Associated Melanotic Schwannoma?

2021 ◽  
pp. 826-831
Author(s):  
Erica M. Roman Hernandez ◽  
Sri Laxmi Valasareddi ◽  
Jarrod Adkison ◽  
Henna Awan ◽  
Krishnamohan R. Basarakodu ◽  
...  
Keyword(s):  
Invasion And Metastasis ◽  
Benign Lesions ◽  
Distinctive Features ◽  
Melanotic Schwannoma ◽  
Disease Modifier ◽  
Malignant Conversion ◽  
Tumor Types ◽  
Generation Sequencing ◽  
Neural Sheath ◽  
Guided Therapy

Melanotic Schwannomas are rare neural sheath tumors with distinctive findings of both Schwann cells and melanocytic cells. Recognition of this entity has prompted the importance of distinction from similar tumor types such as melanomas. Early diagnosis facilitates removal of the mass with less risk of local invasion and metastasis. Although previously known as mostly benign lesions, malignant conversion and recurrence are recognized. This paper presents a patient with melanotic schwannoma, describes the distinctive features that will separate it from melanoma, and addresses the possibility of further guided therapy through next-generation sequencing.

scholarly journals Lavage of the Uterine Cavity for Molecular Detection of Müllerian Duct Carcinomas: A Proof-of-Concept Study

2015 ◽  
Vol 33 (36) ◽  
pp. 4293-4300 ◽  
Author(s):  
Elisabeth Maritschnegg ◽  
Yuxuan Wang ◽  
Nina Pecha ◽  
Reinhard Horvat ◽  
Els Van Nieuwenhuysen ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Tissue ◽  
Massively Parallel Sequencing ◽  
Uterine Cavity ◽  
Mullerian Duct ◽  
Next Generation ◽  
Benign Lesions ◽  
Cavity Detection ◽  
Müllerian Duct ◽  
Generation Sequencing

Purpose Type II ovarian cancer (OC) and endometrial cancer (EC) are generally diagnosed at an advanced stage, translating into a poor survival rate. There is increasing evidence that Müllerian duct cancers may exfoliate cells. We have established an approach for lavage of the uterine cavity to detect shed cancer cells. Patients and Methods Lavage of the uterine cavity was used to obtain samples from 65 patients, including 30 with OC, five with EC, three with other malignancies, and 27 with benign lesions involving gynecologic organs. These samples, as well as corresponding tumor tissue, were examined for the presence of somatic mutations using massively parallel sequencing (next-generation sequencing) and, in a subset, singleplex analysis. Results The lavage technique could be applied successfully, and sufficient amounts of DNA were obtained in all patients. Mutations, mainly in TP53, were identified in 18 (60%) of 30 lavage samples of patients with OC using next-generation sequencing. Singleplex analysis of mutations previously determined in corresponding tumor tissue led to further identification of six patients. Taken together, in 24 (80%) of 30 patients with OC, specific mutations could be identified. This also included one patient with occult OC. All five analyzed lavage specimens from patients with EC harbored mutations. Eight (29.6%) of 27 patients with benign lesions tested positive for mutations, six (75%) as a result of mutations in the KRAS gene. Conclusion This study proved that tumor cells from ovarian neoplasms are shed and can be collected via lavage of the uterine cavity. Detection of OC and EC and even clinically occult OC was achieved, making it a potential tool of significant promise for early diagnosis.

scholarly journals Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of External Ventricular and Lumbar Drainage-Associated Ventriculitis and Meningitis

2020 ◽  
Vol 11 ◽  
Author(s):  
Lingye Qian ◽  
Yijun Shi ◽  
Fangqiang Li ◽  
Yufei Wang ◽  
Miao Ma ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Next Generation Sequencing ◽  
Staphylococcus Epidermidis ◽  
Coincidence Rate ◽  
Next Generation ◽  
Lumbar Drainage ◽  
Gram Positive Bacteria ◽  
Neurosurgical Patients ◽  
Generation Sequencing ◽  
Guided Therapy

Metagenomic next-generation sequencing (mNGS) has become a widely used technology that can accurately detect individual pathogens. This prospective study was performed between February 2019 and September 2019 in one of the largest clinical neurosurgery centers in China. The study aimed to evaluate the performance of mNGS on cerebrospinal fluid (CSF) from neurosurgical patients for the diagnosis of external ventricular and lumbar drainage (EVD/LD)-associated ventriculitis and meningitis (VM). We collected CSF specimens from neurosurgical patients with EVD/LD for more than 24 h to perform conventional microbiological studies and mNGS analyses in a pairwise manner. We also investigated the usefulness of mNGS of CSF for the diagnosis of EVD/LD-associated VM. In total, 102 patients were enrolled in this study and divided into three groups, including confirmed VM (cVM) (39), suspected VM (sVM) (49), and non-VM (nVM) (14) groups. Of all the patients, mNGS detected 21 Gram-positive bacteria, 20 Gram-negative bacteria, and five fungi. The three primary bacteria detected were Staphylococcus epidermidis (9), Acinetobacter baumannii (5), and Staphylococcus aureus (3). The mNGS-positive coincidence rate of confirmed EVD/LD-associated VM was 61.54% (24/39), and the negative coincidence rate of the nVM group was 100% (14/14). Of 15 VM pathogens not identified by mNGS in the cVM group, eight were negative with mNGS and seven were inconsistent with the conventional microbiological identification results. In addition, mNGS identified pathogens in 22 cases that were negative using conventional methods; of them, 10 patients received a favorable clinical treatment; thus, showing the benefit of mNGS-guided therapy.

scholarly journals Analysis of MDM2 Amplification: Next-Generation Sequencing of Patients With Diverse Malignancies

2018 ◽  
pp. 1-14 ◽  
Author(s):  
Shumei Kato ◽  
Jeffrey S. Ross ◽  
Laurie Gay ◽  
Farshid Dayyani ◽  
Jason Roszik ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Mapk Signaling ◽  
Small Subset ◽  
Next Generation ◽  
Investigational Agent ◽  
Mutation Burden ◽  
Tumor Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Mdm2 Amplification

Purpose MDM2 amplification can promote tumorigenesis directly or indirectly through p53 inhibition. MDM2 has increasing clinical relevance because inhibitors are under evaluation in clinical trials, and MDM2 amplification is a possible genomic correlate of accelerated progression, known as hyperprogression, after anti–PD-1/PD-L1 immunotherapy. We used next-generation sequencing (NGS) to ascertain MDM2 amplification status across a large number of diverse cancers. Methods We interrogated the molecular profiles of 102,878 patients with diverse malignancies for MDM2 amplification and co-altered genes using clinical-grade NGS (182 to 465 genes). Results MDM2 amplification occurred in 3.5% of patients (3,650 of 102,878). The majority of tumor types had a small subset of patients with MDM2 amplification. Most of these patients (99.0% [3,613/3,650]) had co-alterations that accompanied MDM2 amplification. Various pathways, including those related to tyrosine kinase (37.9% [1,385 of 3,650]), PI3K signaling (25.4% [926 of 3,650]), TP53 (24.9% [910 of 3,650]), and MAPK signaling (23.6% [863 of 3,650]), were involved. Although infrequent, mismatch repair genes and PD-L1 amplification also were co-altered (2.2% [79 of 3,650]). Most patients (97.6% [3,563 of 3,650]) had one or more co-alterations potentially targetable with either a Food and Drug Administration–approved or investigational agent. MDM2 amplifications were less frequently associated with high tumor mutation burden compared with the MDM2 wild-type population (2.9% v 6.5%; P < .001). An illustrative patient who harbored MDM2 amplification and experienced hyperprogression with an immune checkpoint inhibitor is presented. Conclusion MDM2 amplification was found in 3.5% of 102,878 patients, 97.6% of whom harbored genomic co-alterations that were potentially targetable. This study suggests that a small subset of most tumor types have MDM2 amplification as well as pharmacologically tractable co-alterations.

scholarly journals Zombies in TCGA

2015 ◽  
Vol 89 (8) ◽  
pp. 4044-4046 ◽  
Author(s):  
Daniel DiMaio
Keyword(s):  
Human Papillomavirus ◽  
Next Generation Sequencing ◽  
Hela Cells ◽  
Somatic Mutations ◽  
Hpv Infection ◽  
Next Generation ◽  
Human Cancers ◽  
Human Papillomavirus 18 ◽  
Tumor Types ◽  
Generation Sequencing

Next-generation sequencing results obtained to detect somatic mutations in human cancers can also be searched for viruses that contribute to cancer. Recently, human papillomavirus 18 RNA was detected in tumor types not typically associated with HPV infection. Analyses reported in this issue ofJournal of Virologydemonstrate that the apparent presence of HPV18 RNA in these atypical tumors is due in at least some cases to contamination of samples with HeLa cells, which harbor HPV18.

scholarly journals Clinical Targeted Next-Generation Sequencing to Identify Potentially Actionable Alterations in the Majority of Asian Cancer Patients

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 88s-88s
Author(s):  
S.L. Poon ◽  
Y.-J. Lu ◽  
R.-S. Jhou ◽  
Y.-T. Yang ◽  
P.-N. Yu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Hedgehog Signaling ◽  
Next Generation ◽  
Therapeutic Implications ◽  
Targeted Next Generation Sequencing ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Tissues ◽  
Tumor Types ◽  
Generation Sequencing

Background: Clinically innovative genomic diagnostics may expedite the selection of effective targeted therapies if the patient can be stratified correctly based on their unique cancer driven events/pathways during tumorigenesis. Aim: Here, we performed a pan-cancer analysis on the clinical utility of a targeted gene panel, ACTOnco+, in characterizing the prevalence of actionable mutations. Methods: A total of 229 formalin-fixed, paraffin-embedded (FFPE) tissues from 40 tumor types were subjected to next-generation sequencing (NGS) using the Ion Torrent Proton System. All coding exons in 440 cancer-related genes were assessed at average depth of > 800X. Therapeutic implications were based on information obtained from base substitutions, indels, and copy number alterations (CNAs). Results: 58.5% (n=134) patients harbored at least one actionable mutation while CNAs, including homozygous and heterozygous deletions, were detected in 83.9% (n=191) of patients. Across all tumor types, the most frequently altered pathway that can confer either sensitivity or resistance to targeted therapies was PI3K/AKT/mTOR signaling, contributed by PIK3CA and AKT1 activating mutations as well as NF1, NF2, PTEN, TSC1, STK11 and TSC2 inactivating mutations or deletions. In parallel, dysregulation of cell cycle was mostly owing to CCND1, CDK4 and CDK6 amplification and/or loss of CDKN2A. Notably, on top of BRCA1/ 2 mutations, deletion of BRCAness-related genes ( MRE11, RAD50, PALB2, FANCD2, ATM, ATR, CHEK1 and CHEK2) that may result in homologous recombination deficiency (HRD) was observed in 71.4% breast, 70.6% ovarian, 61.0% lung, 58.3% pancreatic, and 52.2% colorectal cancers. Other targetable alterations on receptor tyrosine kinase (RTK), angiogenic and hedgehog signaling pathways were also observed. Conclusion: A comprehensive pathway-based genomic profiling characterized significant actionable alterations across different solid tumors that may play a role in tissue-agnostic tailored treatment.

scholarly journals Somatic genetic alterations in a large cohort of pediatric thyroid nodules

2019 ◽  
Vol 8 (6) ◽  
pp. 796-805 ◽  
Author(s):  
Barbora Pekova ◽  
Sarka Dvorakova ◽  
Vlasta Sykorova ◽  
Gabriela Vacinova ◽  
Eliska Vaclavikova ◽  
...  
Keyword(s):  
High Frequency ◽  
Detection Rate ◽  
Thyroid Nodules ◽  
Pediatric Patients ◽  
Distant Metastases ◽  
Genetic Alterations ◽  
Papillary Thyroid ◽  
Benign Lesions ◽  
Benign Nodules ◽  
Generation Sequencing

There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.

scholarly journals NTRK Fusions Identified in Pediatric Tumors: The Frequency, Fusion Partners, and Clinical Outcome

2021 ◽  
pp. 204-214
Author(s):  
Xiaonan Zhao ◽  
Chelsea Kotch ◽  
Elizabeth Fox ◽  
Lea F. Surrey ◽  
Gerald B. Wertheim ◽  
...  
Keyword(s):  
Pediatric Cancer ◽  
Genomic Profiling ◽  
Pediatric Tumors ◽  
Receptor Kinase ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Dna And Rna ◽  
Tumor Types ◽  
Tyrosine Receptor Kinase ◽  
Generation Sequencing

PURPOSE Neurotrophic tyrosine receptor kinase (NTRK) fusions have been described as oncogenic drivers in a variety of tumors. However, little is known about the overall frequency of NTRK fusion in unselected pediatric tumors. Here, we assessed the frequency, fusion partners, and clinical course in pediatric patients with NTRK fusion–positive tumors. PATIENTS AND METHODS We studied 1,347 consecutive pediatric tumors from 1,217 patients who underwent tumor genomic profiling using custom-designed DNA and RNA next-generation sequencing panels. NTRK fusions identified were orthogonally confirmed. RESULTS AND DISCUSSION NTRK fusions were identified in 29 tumors from 27 patients with a positive yield of 2.22% for all patients and 3.08% for solid tumors. Although NTRK2 fusions were found exclusively in CNS tumors and NTRK1 fusions were highly enriched in papillary thyroid carcinomas, NTRK3 fusions were identified in all tumor categories. The most canonical fusion was ETV6-NTRK3 observed in 10 patients with diverse types of tumors. Several novel NTRK fusions were observed in rare tumor types, including KCTD16-NTRK1 in ganglioglioma and IRF2BP2-NTRK3 in papillary thyroid carcinomas. The detection of an NTRK fusion confirmed the morphologic diagnosis including five cases where the final tumor diagnosis was largely based on the discovery of an NTRK fusion. In one patient, the diagnosis was changed because of the identification of an ETV6-NTRK3 fusion. One patient with infantile fibrosarcoma was treated with larotrectinib and achieved complete pathologic remission. CONCLUSION NTRK fusions are more frequently seen in pediatric tumors than in adult tumors and involve a broader panel of fusion partners and a wider range of tumors than previously recognized. These results highlight the importance of screening for NTRK fusions as part of the tumor genomic profiling for patients with pediatric cancer.

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