scholarly journals YAP1-NUTM1 Gene Fusion in Porocarcinoma of the External Auditory Canal

2020 ◽  
Vol 14 (4) ◽  
pp. 982-990 ◽  
Author(s):  
Abbas Agaimy ◽  
Lars Tögel ◽  
Florian Haller ◽  
Johannes Zenk ◽  
Joachim Hornung ◽  
...  
Keyword(s):  
External Auditory Canal ◽  
Gene Fusion ◽  
Original Description ◽  
Squamous Differentiation ◽  
Aberrant Expression ◽  
Nut Midline Carcinoma ◽  
Ductal Cells ◽  
Children And Young Adults ◽  
Nut Carcinoma ◽  
Generation Sequencing

AbstractGene fusions involving the NUTM1 gene (NUT) represent defining genetic markers of a highly aggressive carcinoma type with predilection for the midline structures of children and young adults, hence the original description as NUT midline carcinoma. Recent studies have increasingly documented involvement of the NUTM1 gene in the pathogenesis of other entities as well. We herein describe two cases of auditory canal carcinomas with features of porocarcinoma, both harboring a newly described YAP1-NUTM1 gene fusion. Patients were males aged 28 and 82 years who presented with slowly growing lesions in the external auditory canal. Histologic examination showed monomorphic basaloid and squamoid cells arranged into organoid solid aggregates, nests, ducts, small cysts, and focal pseudocribriform pattern with variable mitotic activity, infiltrative growth, and focal squamous differentiation, particularly in the most superficial part of the tumor. Immunohistochemistry revealed consistent reactivity for CK5, p63 and SOX10 and diffuse aberrant expression of TP53. CK7 expression was limited to a few luminal ductal cells. The androgen receptor and S100 were negative. Next generation sequencing (TruSight RNA fusion panel, Illumina) revealed the same YAP1-NUTM1 gene fusion in both tumors, which was subsequently confirmed by NUT-FISH and the monoclonal anti-NUT antibody. These cases represent a novel contribution to the spectrum of NUT-rearranged head and neck malignancies. This adnexal carcinoma variant should not be confused with the highly lethal NUT carcinoma based on NUT immunoreactivity alone.

scholarly journals Challenging Diagnosis in NUT Carcinoma

2021 ◽  
pp. 106689692110195
Author(s):  
Grosse Claudia ◽  
Grosse Alexandra
Keyword(s):  
Nuclear Protein ◽  
Hematological Malignancy ◽  
Undifferentiated Carcinoma ◽  
Squamous Differentiation ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated ◽  
Nut Carcinoma ◽  
Disseminated Disease ◽  
Generation Sequencing

Nuclear protein in testis (NUT) carcinoma represents a highly aggressive, poorly differentiated carcinoma that is genetically defined by rearrangement of NUT gene. The histomorphological appearance ranges from entirely undifferentiated carcinoma to carcinoma with prominent squamous differentiation. NUT carcinoma can display neuroendocrine features. Although it is typically distributed along the midline axis, it may manifest in nonmidline locations. The majority of patients develop rapidly disseminated disease. We illustrate 2 cases of NUT carcinoma, one located in the lung, which closely resembled a neuroendocrine carcinoma, and the other one with assumed lung origin demonstrating metastatic dissemination with diffuse bone involvement, which was clinically first suspected to be a hematological malignancy. Due to its undifferentiated nature, NUT carcinoma may be confused with many entities. NUT immunohistochemistry is considered to be sufficient for the diagnosis. Fluorescence in-situ hybridization analysis and next-generation sequencing are currently used to confirm the diagnosis.

BCOR-CCNB3 Sarcoma with Prominent Rhabdoid Cells Mimicking Rhabdomyoblasts: Expanding the Morphologic spectrum of BCOR-CCNB3 Sarcoma

2021 ◽  
pp. 106689692110138
Author(s):  
Zhenjian Cai ◽  
Darryl Duncan ◽  
Rongying Li ◽  
Jaiyeola Thomas ◽  
Hui Zhu
Keyword(s):  
Young Adults ◽  
Next Generation Sequencing ◽  
Gene Fusion ◽  
Correct Diagnosis ◽  
Undifferentiated Sarcoma ◽  
Rhabdoid Cells ◽  
Eosinophilic Cytoplasm ◽  
Children And Young Adults ◽  
Variable Morphology ◽  
Generation Sequencing

BCOR-CCNB3 sarcoma (BCS) is a rare recently defined undifferentiated sarcoma that predominantly affects children and young adults. The diagnosis of this tumor is difficult due to the highly variable morphology and nonspecific immunophenotype. Emerging data suggest that patients with BCS show response to Ewing sarcoma-based treatment regimen, thus correct diagnosis is of clinical relevance. In this study, we report a case of BCS arising from the big toe of a 15-year-old male patient. The tumor had a prominent population of rhabdoid cells with bright eosinophilic cytoplasm mimicking rhabdomyosarcoma. The tumor cells were focally positive for desmin and myogenin, and negative for CD99. Next-generation sequencing showed the presence of BCOR-CCNB3 gene fusion. BCS with prominent rhabdoid cells has not been described before. This study further expands the morphologic spectrum of BCS.

scholarly journals Disseminated non-Langerhans cell histiocytosis with an IRF2BP2-NTRK1 gene fusion identified by next-generation sequencing

2020 ◽  
Vol 6 (11) ◽  
pp. 1156-1158
Author(s):  
Warren H. Chan ◽  
Aatman Shah ◽  
Gordon Bae ◽  
Caely Hambro ◽  
Beth A. Martin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Langerhans Cell Histiocytosis ◽  
Gene Fusion ◽  
Langerhans Cell ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Aberrant Expression of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) in Warthin Tumors

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1112 ◽  
Author(s):  
Robert Mandic ◽  
Abbas Agaimy ◽  
Daniel Pinto-Quintero ◽  
Katrin Roth ◽  
Afshin Teymoortash ◽  
...  
Keyword(s):  
Parotid Gland ◽  
Normal Control ◽  
Staining Pattern ◽  
Rna Extraction ◽  
Renal Oncocytoma ◽  
Mrna Levels ◽  
Warthin Tumor ◽  
Aberrant Expression ◽  
Ductal Cells ◽  
Gapdh Mrna

The Warthin tumor represents the second most frequent benign tumor of the parotid gland and is characterized by the presence of oncocytes rich in structurally and functionally altered mitochondria. Next to its role in metabolism, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is also implicated in cellular mitophagy. Immunohistochemistry was carried out on Warthin tumor and normal control (parotid gland with striated ducts) tissues, using anti-GAPDH specific antibodies followed by digital image analysis. Laser capture microdissection was used to isolate the oncocytic tumor cell and normal control striated duct compartments for RNA extraction and qPCR. Warthin tumor oncocytes exhibited a markedly spotted GAPDH staining pattern exhibiting cells with cytoplasmic and nuclear, only nuclear or none GAPDH staining. A significantly lower (p < 0.0001) total GAPDH signal was detected in Warthin tumor oncocytes. Similarly, significantly lower (p < 0.005) GAPDH mRNA levels were seen in oncocytes compared with normal ductal cells. To exclude the possibility of this GAPDH staining pattern being a general feature of oncocytic neoplasms of different organs, we tested a cohort of renal oncocytoma and oncocytic chromophobe carcinoma; none showed this type of staining. The observed progressive GAPDH loss in Warthin tumor oncocytes could be implicated in the pathogenesis of Warthin tumors.

scholarly journals A rare case of recurrent ovarian cancer with NTRK1-TPM3 gene rearrangement

2021 ◽  
Author(s):  
Yuta Endo ◽  
Takafumi Watanabe ◽  
Motonobu Saito ◽  
Katsuharu Saito ◽  
Rei Suzuki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Fusion ◽  
Rare Case ◽  
Multimodal Therapy ◽  
Gynecologic Cancer ◽  
Stage Iv ◽  
Recurrent Ovarian Cancer ◽  
Interval Debulking Surgery ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: NTRK gene fusion is rare in gynecologic cancer. Entrectinib is a novel targeted drug which is a potent inhibitor of TRK A, B and C. Here, we present a case of recurrent ovarian cancer with NTRK1-TPM3 rearrangement, which was detected by next-generation sequencing (NGS) and treated with entrectinib. Case Presentation:A 56-year-old woman was diagnosed as having stage IV ovarian cancer due to pleural effusion. Neoadjuvant chemotherapy and interval debulking surgery followed by chemotherapy were performed. Ten months after completion of chemotherapy, the patient’s disease recurred. She was treated with multimodal therapy for recurrence. DNA-based NGS detected NTRK1-TPM3 rearrangement and entrectinib was started. However, the patient’s disease progressed despite six weeks’ administration of entrectinib, and one month after discontinuation of entrectinib, she died. After her death immunohistochemistry with a pan-Trk monoclonal antibody was performed to determine the expression of NTRK. However, immunohistochemistry was negative for NTRK.Conclusion: We presented a rare case of recurrent ovarian cancer with NTRK1-TPM3 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA-based NGS, immunohistochemistry was negative for NTRK. Immunohistchemitory should be performed for confirmation of NTRK protein expression before entrectinib administration.

scholarly journals Next Generation Sequencing for Gene Fusion Analysis in Lung Cancer: A Literature Review

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 521
Author(s):  
Rossella Bruno ◽  
Gabriella Fontanini
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Gene Fusion ◽  
Repetitive Sequences ◽  
Clinical Samples ◽  
Gene Fusions ◽  
Next Generation ◽  
Hybrid Capture ◽  
Fusion Analysis ◽  
Generation Sequencing

Gene fusions have a pivotal role in non-small cell lung cancer (NSCLC) precision medicine. Several techniques can be used, from fluorescence in situ hybridization and immunohistochemistry to next generation sequencing (NGS). Although several NGS panels are available, gene fusion testing presents more technical challenges than other variants. This is a PubMed-based narrative review aiming to summarize NGS approaches for gene fusion analysis and their performance on NSCLC clinical samples. The analysis can be performed at DNA or RNA levels, using different target enrichment (hybrid-capture or amplicon-based) and sequencing chemistries, with both custom and commercially available panels. DNA sequencing evaluates different alteration types simultaneously, but large introns and repetitive sequences can impact on the performance and it does not discriminate between expressed and unexpressed gene fusions. RNA-based targeted approach analyses and quantifies directly fusion transcripts and is more accurate than DNA panels on tumor tissue, but it can be limited by RNA quality and quantity. On liquid biopsy, satisfying data have been published on circulating tumor DNA hybrid-capture panels. There is not a perfect method for gene fusion analysis, but NGS approaches, though still needing a complete standardization and optimization, present several advantages for the clinical practice.

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