RNA-Based next generation sequencing complements but does not replace fluorescence in situ hybridization studies for the classification of aggressive B-Cell lymphomas

Context.— Tumors harboring CIC-NUTM1 fusion are a newly recognized rare sarcoma, but the documented cases are still limited. It is unclear whether it is the same as classic CIC-DUX4 sarcoma in terms of its clinical, pathologic, and behavioral aspects. Objective.— To further explore the clinicopathologic characteristics of CIC-NUTM1 sarcoma. Design.— The cases were diagnosed based on immunophenotype, next-generation sequencing, and fluorescence in situ hybridization tests and compared with the reported CIC-NUTM1 sarcomas in the literature. Results.— Three cases of CIC-NUTM1 sarcomas involving the spine in adults were described. They were 2 men and 1 woman, aged 38 to 61 years. Two tumors were located in thoracic vertebrae and 1 in a cervical vertebra. All were locally advanced lesions destroying the bone and soft tissues without spinal cord involvement or metastasis. The tumors were composed of monomorphic small to medium-sized cells with round to epithelioid appearance. The architecture was lobulated and solid with diffuse or multifocal myxoid stroma. Next-generation sequencing revealed an in-frame fusion between CIC (exon 16 or 17) and NUTM1 (exon 5 or 6) in 3 cases. Fluorescence in situ hybridization confirmed CIC and NUTM1 breaks, and immunohistochemistry showed NUT staining in the nucleus. The patients died of disease 8 to 15 months (mean, 10.7 months) after presentation. Of the CIC-NUTM1 sarcomas reported in the literature along with our cases (n = 11), 8 cases developed in axial bone (5 spine, 3 skull base). Conclusions.— CIC-NUTM1 sarcomas showed distinct anatomic tropism for the axial skeleton and unfavorable behavior compared with classic CIC sarcoma.

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ALK Gene Rearrangements in Lung Adenocarcinomas: Concordance of Immunohistochemistry, Fluorescence In Situ Hybridization, RNA In Situ Hybridization, and RNA Next-Generation Sequencing Testing

JTO Clinical and Research Reports ◽

10.1016/j.jtocrr.2021.100223 ◽

2021 ◽

Vol 2 (10) ◽

pp. 100223

Author(s):

Carleigh R. Canterbury ◽

Helen Fernandes ◽

John P. Crapanzano ◽

Vundavalli V. Murty ◽

Mahesh M. Mansukhani ◽

...

Keyword(s):

In Situ Hybridization ◽

Next Generation Sequencing ◽

Fluorescence In Situ Hybridization ◽

Gene Rearrangements ◽

Next Generation ◽

Rna In Situ Hybridization ◽

Lung Adenocarcinomas ◽

Generation Sequencing

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Comparison Between Integrated Genomic DNA/RNA Profiling and Fluorescence In Situ Hybridization in the Detection of MYC, BCL-2, and BCL-6 Gene Rearrangements in Large B-Cell Lymphomas

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz172 ◽

2019 ◽

Vol 153 (3) ◽

pp. 353-359 ◽

Cited By ~ 1

Author(s):

Daniel P Cassidy ◽

Jennifer R Chapman ◽

Rafael Lopez ◽

Kyle White ◽

Yao-Shan Fan ◽

...

Keyword(s):

In Situ Hybridization ◽

B Cell ◽

Fluorescence In Situ Hybridization ◽

Genomic Dna ◽

Standard Of Care ◽

Gene Rearrangements ◽

B Cell Lymphomas ◽

Rna Profiling ◽

Large B Cell

Abstract Objectives To compare fluorescence in situ hybridization (FISH) and a commercially available sequencing assay for comprehensive genomic profiling (CGP) to determine the best approach to identify gene rearrangements (GRs) in large B-cell lymphomas (LBCLs). Methods Comparison of standard-of-care FISH assays (including a two-probe approach for MYC; break-apart and fusion probes) and an integrated genomic DNA/RNA sequencing CGP approach on a set of 69 consecutive LBCL cases. Results CGP detected GRs, including those involving MYC (1), BCL-2 (3), and BCL-6 (3), not detected by FISH. FISH detected non–IgH-MYC (4) and BCL-6 (2) GRs that were not detected by CGP. In four instances, standalone CGP or FISH testing would have missed a double-hit lymphoma. Conclusions CGP was superior to FISH in the detection of IgH-MYC rearrangements but was inferior for the detection of non–IgH-MYC rearrangements. Our study demonstrates the rationale for development of a customized approach to identify GRs in LBCLs.

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