Characterization of NTRK gene fusion events in solid tumors among Chinese patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15040-e15040
Author(s):  
Xuhui Zhang ◽  
Dongsheng Chen ◽  
Qin Zhang ◽  
Qianqian Duan ◽  
Qing WANG ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Chinese Patients ◽  
Fusion Partner ◽  
Gene Fusions ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Partner Characteristics ◽  
Exon 20 ◽  
Tumor Types

e15040 Background: NTRK fusions are actionable genomic alterations detected across tumor types. NTRK gene fusions involving either NTRK1, NTRK2 or NTRK3 (encoding the neurotrophin receptors TRKA, TRKB and TRKC, respectively) are oncogenic drivers of various adult and paediatric tumour types. Here, we update the detection of NTRK gene fusions across tumor types and further describe fusion partner characteristics among Chinese patients. Methods: Samples submitted for clinical molecular profiling were retrospectively analyzed for NTRK fusion events. Method for identifying NTRK fusions was DNA-based next-generation sequencing that tumour DNA is extracted from formalin-fixed paraffin-embedded tissue. All NTRK fusion partners were identified for intact functional domains, domain prediction, breakpoints, frame retention and co-occurring alterations. Results: A total of 64 NTRK fusion events (0.26% of 24,451) were identified. NTRK fusions are characteristic in a few rare types of cancer, such as melanoma, glioma and carcinomas of the thyroid, lung and colon, but they are also infrequently seen in some uncommon cancers, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma. Among the fusions, NTRK1 (0.08% of 24,430), NTRK2 (0.02% of 24,445), NTRK3 (0.15% of 24,414) were identified. Twenty-six unique fusion partners were identified, the most common in NTRK1 fusion being TPM3 (23.8%), NTRK2 fusion being AGTPBP1 (33.3%), and NTRK3 fusion being TFG (13.5%). Almost 53.8 % (14 of 26) of all fusion events are expected to include the transmembrane domain contributed by the NTRK fusion partner. The most commonly identified breakpoints occur in exon 14 and exon 17 and in exon 15 and exon 20, in NTRK1, NTRK3, respectively. Conclusions: NTRK fusion products are diverse across tumor types, but the significance of these variations is not clear. The biological and clinical implications of retaining certain domains of NTRK and of fusion partners warrants further investigation.

Characterization of NRG1 gene fusion events in solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3113-3113
Author(s):  
Sushma Jonna ◽  
Rebecca Feldman ◽  
Sai-Hong Ignatius Ou ◽  
Misako Nagasaka ◽  
Jeffrey Swensen ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Fusion Partner ◽  
Exon 2 ◽  
Downstream Signaling ◽  
Chimeric Transcripts ◽  
Exon 1 ◽  
Tumor Types ◽  
Fusion Products ◽  
Ig Domain

3113 Background: NRG1 fusions are actionable genomic alterations detected across tumor types. The NRG1 gene encode for neuregulin, which serves as a ligand for ERBB3 and ERBB4 receptors and activates downstream signaling through the MAPK and PI3K pathways. Here, we update the detection of NRG1 gene fusions across tumor types and further describe fusion characteristics. Methods: Samples submitted for clinical molecular profiling that included RNA-sequencing (Archer Dx or Caris MI transcriptome) were retrospectively analyzed for NRG1 fusion events. All NRG1 fusions with ≥ 3 junction reads were identified for manual review and for characterization of fusion class, intact functional domains, domain prediction, breakpoints, frame retention and co-occurring alterations by NGS. Results: A total of 82 NRG1 fusion events (0.2% of 44,570) were identified. Among the fusions identified, the distribution across tumor types was as follows: non-small cell lung cancer (NSCLC, 54%), breast cancer (11%), ovarian cancer (7%), pancreatic cancer (7%), cholangiocarcinoma (6%), colorectal cancer (5%), and other (10%). Forty-two unique fusion partners were identified, the most common being CD74 (23%), ATP1B1 (9%), SLC3A2 (7%), RBPMS (6%) and SDC4 (4%). Almost half (47%) of all fusion events are expected to include the transmembrane domain contributed by the NRG1 fusion partner. Lung and pancreatobilliary cancers had the highest rates of transmembrane domain retention from their fusion partners (63.6% and 54.5%, respectively). In all other tumor groups, most fusion partners lacked transmembrane domains. In 15% of cases, the chimeric transcripts are predicted to lead to increased expression of NRG1. The most commonly reported breakpoints in NRG1 occur in exon 6 and exon 2. While fusions with the NRG1 breakpoint at exon 2 retain the immunoglobulin (Ig) domain and all downstream portions (including EGF-like domain), those at exon 6 do not contain the Ig portion and result in shorter chimeric proteins. The breakpoints in all CD74:NRG1 fusions, the most common fusions in NSCLC, occur at exon 5 or 6 and cause truncation of domains upstream of the EGF-like domain. In ATP1B1:NRG1 fusions, the most common fusions in pancreatobilliary cancers, the breakpoints are at exon 1 or 2 and retain the Ig domain. Conclusions: NRG1 fusion products are diverse across tumor types, but the significance of these variations is not clear. The biological and clinical implications of retaining certain domains of NRG1 (such as the Ig domain) and of fusion partners warrants further investigation.

scholarly journals Characterization of epididymal and testicular histologic lesions and use of immunohistochemistry and PCR on formalin-fixed tissues to detect Brucella canis in male dogs

2021 ◽  
pp. 104063872098688
Author(s):  
Andrea M. Camargo-Castañeda ◽  
Lauren W. Stranahan ◽  
John F. Edwards ◽  
Daniel G. Garcia-Gonzalez ◽  
Leonardo Roa ◽  
...  
Keyword(s):  
Accurate Diagnosis ◽  
Testicular Atrophy ◽  
Detection Techniques ◽  
Formalin Fixed Paraffin ◽  
Brucella Canis ◽  
Formalin Fixed Paraffin Embedded ◽  
Variable Sensitivity ◽  
Ffpe Tissues ◽  
Formalin Fixed

In male dogs, Brucella canis frequently causes epididymitis, ultimately resulting in testicular atrophy and infertility. Although B. canis predominantly affects the epididymis, the misleading term “orchitis” is still commonly used by clinicians. Of additional concern, diagnosis in dogs remains challenging because of variable sensitivity and specificity of serologic assays and fluctuations in bacteremia levels in infected dogs, reducing the sensitivity of blood culture. We describe here the histologic lesions in the scrotal contents of 8 dogs suspected of being infected with B. canis and clinically diagnosed with orchitis. We explored the possibility of using immunohistochemistry (IHC) and real-time PCR (rtPCR) in formalin-fixed, paraffin-embedded (FFPE) tissues to detect the presence of B. canis. Epididymitis of variable chronicity was identified in all 8 dogs, with only 3 also exhibiting orchitis. Using rtPCR, the presence of B. canis was identified in 4 of 8 dogs, with 3 of these 4 dogs also positive by IHC. These results suggest that rtPCR and IHC are promising techniques that can be used in FFPE tissues to detect B. canis when other detection techniques are unavailable. Additionally, accurate recognition of epididymitis rather than orchitis in suspect cases could aid in accurate diagnosis.

scholarly journals Molecular Profiles and Metastasis Markers in Chinese Patients with Gastric Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chao Chen ◽  
Chunmei Shi ◽  
Xiaochun Huang ◽  
Jianwei Zheng ◽  
Zhongyi Zhu ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Chinese Patients ◽  
Tissue Samples ◽  
Whole Exome ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
High Concordance ◽  
Predictive Role ◽  
Molecular Profiles ◽  
Genomic Regions

Abstract The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. PTPRT is significantly associated with metastasis of GC, suggesting its predictive role in metastasis of GC. Patients carrying BRCA2 mutations tend not to metastasize, which may be related to their sensitivity to chemotherapy. Mutations in MACF1, CDC27, HMCN1, CDH1 and PDZD2 were moderately enriched in peritoneal metastasis (PM) samples. Furthermore, we found two genomic regions (1p36.21 and Xq26.3) were associated with PM of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (P = 0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies.

SOX2 Expression in Canine Neoplasia

2020 ◽  
pp. 030098582096013
Author(s):  
Ileana C. Miranda ◽  
Andrew D. Miller
Keyword(s):  
Rational Design ◽  
Prognostic Indicator ◽  
Screening Methods ◽  
Tumor Type ◽  
Sox2 Expression ◽  
Formalin Fixed Paraffin ◽  
Normal Expression ◽  
Formalin Fixed Paraffin Embedded ◽  
Stem Cell Pluripotency ◽  
Tumor Types

SOX2 is a major transcriptional regulator of stem cell pluripotency and self-renewability. Its expression in cancer stem cells from several different tumor types in humans and rodent models directly implicates SOX2 in tumorigenicity, metastasis, drug resistance, recurrence, and poor survival. Our objective was to investigate the expression of SOX2 in canine neoplasia. Immunohistochemistry for SOX2 was performed in sets of 10 archived formalin-fixed paraffin-embedded tissues from 45 distinct canine neoplasms. Normal expression of SOX2 was evaluated in a canine tissue microarray. Strong and diffuse SOX2 intranuclear immunolabeling was consistently found in the majority of ectodermal (13/15) and endodermal tumors (5/7). Negative, variable, or inconsistent SOX2 intranuclear immunolabeling was detected in the majority of mesodermal tumors (10/16) and in tumors with dual or uncertain origin (5/7). Although further studies are necessary to understand mechanistically how SOX2 contributes to the biology of each tumor type, this study demonstrates the expression of SOX2 in a wide variety of canine cancers. In the future, screening methods based on cellular plasticity and pluripotency biomarkers may provide avenues for the rational design of therapeutic strategies that target vulnerable signals upstream or downstream of SOX2 in different cancers, and possibly offer novel clinical applications for SOX2 as a prognostic indicator.

scholarly journals PTM-Shepherd: analysis and summarization of post-translational and chemical modifications from open search results

2020 ◽  
pp. mcp.TIR120.002216
Author(s):  
Daniel J. Geiszler ◽  
Andy T. Kong ◽  
Dmitry M Avtonomov ◽  
Fengchao Yu ◽  
Felipe da Veiga Leprevost ◽  
...  
Keyword(s):  
Shotgun Proteomics ◽  
Chemical Modifications ◽  
Bioinformatics Tool ◽  
Site Specific ◽  
Search Results ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Small Set ◽  
Formalin Fixed

Open searching has proven to be an effective strategy for identifying both known and unknown modifications in shotgun proteomics experiments. Rather than being limited to a small set of user-specified modifications, open searches identify peptides with any mass shift that may correspond to a single modification or a combination of several modifications. Here we present PTM-Shepherd, a bioinformatics tool that automates characterization of PTM profiles detected in open searches based on attributes such as amino acid localization, fragmentation spectra similarity, retention time shifts, and relative modification rates. PTM-Shepherd can also perform multi-experiment comparisons for studying changes in modification profiles, e.g. in data generated in different laboratories or under different conditions. We demonstrate how PTM-Shepherd improves the analysis of data from formalin-fixed paraffin-embedded samples, detects extreme underalkylation of cysteine in some datasets, discovers an artefactual modification introduced during peptide synthesis, and uncovers site-specific biases in sample preparation artifacts in a multi-center proteomics profiling study.

Sign in / Sign up

Export Citation Format

Share Document