Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring

Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of p...

Full description

Saved in:
Bibliographic Details
Published in:Cancers Vol. 14; no. 20; p. 5152
Main Authors: Schrader, Anne M. R, de Groen, Ruben A. L, Willemze, Rein, Jansen, Patty M, Quint, Koen D, Cleven, Arjen H. G, van Wezel, Tom, van Eijk, Ronald, Ruano, Dina, Veelken, J. H. (Hendrik), Tensen, Cornelis P, Neelis, Karen J, Daniels, Laurien A, Hauben, Esther, Woei-A-Jin, F. J. S. H. (Sherida), Busschots, A. M. (Annemie), Vermeer, Maarten H, Vermaat, Joost S. P
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-10-2022
MDPI
Subjects:
B-cell lymphoma
Biopsy
Cancer
Care and treatment
Cloning
Confidence intervals
Evolution & development
Genetic aspects
Leg
Lymphocytes B
Lymphoma
Lymphomas
Medical imaging
Methods
Mutation
Mutation hot spots
Myc protein
MyD88 protein
Next-generation sequencing
Patient monitoring
Patients
Radiation therapy
Relapse
Remission (Medicine)
Skin
Tomography
Netherlands
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14205152