- •Atypical MYC FISH signal patterns (5’MYC or 3’MYC gain/loss) are not equivalent to unbalanced MYC-R.
- •5’MYC gain often associates with refractory to chemotherapy and short event-free survival and likely represents an unbalanced MYC-R.
- •3’MYC loss is not associated with poor prognosis and may not represent MYC-R.
FISH analysis using MYC break-apart probes is a widely used technique to assess for MYC rearrangement (MYC-R). Occasionally, FISH results in atypical signal patterns, such as gain or loss of 5ʹMYC or 3ʹMYC. The clinical impact and/or relationship of these atypical signal patterns to MYC-R are unknown. In this study, we assessed 35 patients who had aggressive B-cell lymphomas and exhibited atypical FISH signal patterns: 3ʹMYC deletion (n = 16) or 3ʹMYC deletion plus 5ʹMYC amplification (n = 5), 5ʹMYC gain (n = 10), 5ʹMYC deletion (n = 3), and 3ʹMYC gain (n = 1). For comparison, we also included 9 patients who showed an unbalanced MYC-R. Patients with 5ʹMYC gain showed MYC expression and were often refractory to chemotherapy (n = 7) or had early relapse (n = 2). By contrast, lymphomas with 3ʹMYC deletion were negative or had low expression of MYC (16 of 18), and patients often responded to chemotherapy (16 of 19). The median event-free survival was 24, 6, and 4 months for patients with 3ʹMYC deletion, 5ʹMYC gain and unbalanced MYC-R, respectively (p = 0.0048). We conclude that 5ʹMYC gain is associated with MYC expression and a poorer prognosis and likely represents an unbalanced MYC-R. By contrast, 3ʹMYC deletions are not associated with MYC expression or a poorer prognosis and this finding may be unrelated to MYC-R.
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- Diffuse large B-Cell lymphoma.N Engl J Med. 2021; 384: 842-858
- Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte.Blood. 2010; 116: 2040-2045
- Prognostic significance of MYC Rearrangement and translocation partner in diffuse large B-cell lymphoma: a study by the lunenburg lymphoma biomarker consortium.J Clin Oncol. 2019; 37: 3359-3368
- MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy.Blood. 2009; 114: 3533-3537
- Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab.J Clin Oncol. 2010; 28: 3360-3365
- Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.Mod Pathol. 2014; 27: 958-971
- MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.Blood. 2015; 126: 2466-2474
- WHO classification of tumours of haematopoietic and lymphoid tissues, revised.4th edition. International Agency for Research on Cancer, Lyon, France2017
- The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms.Leukemia. 2022; 36: 1720-1748
- First-line treatment of double-hit and triple-hit lymphomas: survival and tolerance data from a retrospective multicenter French study.Am J Hematol. 2021; 96: 302-311
- Double hit lymphoma: the MD Anderson Cancer Center clinical experience.Br J Haematol. 2014; 166: 891-901
- Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.Blood. 2014; 124: 2354-2361
- Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas.Leukemia. 2007; 21: 515-523
- Identification of two distinct MYC breakpoint clusters and their association with various IGH breakpoint regions in the t(8;14) translocations in sporadic Burkitt-lymphoma.Leukemia. 2007; 21: 1739-1751
- Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate c-myc and the IgH locus up to several hundred kb.Hum Mol Genet. 1992; 1: 625-632
- High-resolution architecture and partner genes of MYC rearrangements in lymphoma with DLBCL morphology.Blood Adv. 2018; 2: 2755-2765
- MYC break-apart FISH probe set reveals frequent unbalanced patterns of uncertain significance when evaluating aggressive B-cell lymphoma.Blood Cancer J. 2021; 11: 184
- High-grade B-cell lymphoma with MYC rearrangement and without BCL2 and BCL6 rearrangements is associated with high P53 expression and a poor prognosis.Am J Surg Pathol. 2016; 40: 253-261
- Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray.Blood. 2004; 103: 275-282
- MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.Mod Pathol. 2018; 31: 1470-1478
- Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.J Clin Oncol. 2014; 32: 1066-1073
- Elucidating a false-negative MYC break-apart fluorescence in situ hybridization probe study by next-generation sequencing in a patient with high-grade B-cell lymphoma with IGH/MYC and IGH/BCL2 rearrangements.Cold Spring Harb Mol Case Stud. 2019; 5
- Author Correction: A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies.Nature. 2018; 558: E4
- MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is associated with characteristic clinicopathological findings and TP53 gene mutation.Hum Pathol. 2015; 46: 65-73
- Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study.Haematologica. 2013; 98: 255-263
- Prognostic significance of MYC rearrangement and translocation partner in diffuse large B-cell lymphoma: a study by the lunenburg lymphoma biomarker consortium.J Clin Oncol. 2019; 37: 3359-3368
- Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements.Haematologica. 2018; 103: 1899-1907
- Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.J Clin Oncol. 2012; 30: 3460-3467
- MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.Haematologica. 2013; 98: 1554-1562
Published online: December 18, 2022
Accepted: December 17, 2022
Received in revised form: November 7, 2022
Received: September 15, 2022
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