DNA copy number imbalances in primary cutaneous lymphomas

Abstract

Background Cutaneous lymphomas (CL) represent a clinically defined group of extranodal non‐Hodgkin lymphomas harbouring heterogeneous and incompletely delineated molecular aberrations. Over the past decades, molecular studies have identified several chromosomal aberrations, but the interpretation of individual genomic studies can be challenging. Objective With a comprehensive meta‐analysis, we aim to delineate genomic alterations for different types of CL and propose a more accurate classification in line with their various pathogenicity. Methods We searched PubMed and ISI Web of Knowledge for publications from 1996 to 2016 reporting the investigation of CL for genome‐wide copy number alterations, by means of comparative genomic hybridization techniques and whole‐genome sequencing and whole‐exome sequencing. We then extracted and remapped the available copy number variation (CNV) data from these publications with the same pipeline and performed clustering and visualisation to aggregate samples of similar CNV profiles. Results For 449 samples from 22 publications, CNV data were accessible for sample based meta‐analysis. Our findings illustrate structural and numerical chromosomal imbalance patterns. Most frequent CNAs were linked to oncogenes or tumour suppressor genes with important roles in the course of the disease. Conclusion Summary profiles for genomic imbalances, generated from case‐specific data, identified complex genomic imbalances, which could discriminate between different subtypes of CL and promise a more accurate classification. The collected data presented in this study are publicly available through the ‘Progenetix’ online repository.

Branched evolution and genomic intratumor heterogeneity in the pathogenesis of cutaneous T-cell lymphoma

“…30,31 We also investigated the CNA profiles for all our samples ( Fig 3A ) and were able to confirm the previously noted amplifications of chromosome 1 and 7 and deletions in chromosome 9 in MF. 32 The patterns of changes in the CNA profiles were similar for samples TMR and LSP but different from ESP that surprisingly was characterised by larger CNA fragments and increased number of copy number gains across all chromosomes except 6, 9,13, 19 and 21 ( Fig 3A ). We have also analyzed CNA changes in the putative driver genes.…”

From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis

“…Deletions on the short arm (p) and the deletion of the p53 gene described in other studies are seen in neither of our MF or LPP samples [ 10 ]. This could have happened because of the relatively small group of patients.…”

“…To date, several genetic abnormalities have been highlighted in MF, with gains being described more often than deletions in relation to copy number alterations (CNAs) [ 10 ]. Gains were emphasized to affect chromosomes 1, 7, 8, 9qter, 17, 19, 22 and losses on the chromosomes 6q, 9pter, 10, 13q, 16q and 17p [ 10 ].…”

“…Downregulations of the FAS gene (10q23.31), which modulates the caspase cascade and tumor suppressor PTEN (10q23.31), are described in numerous CTCLs [ 10 , 29 , 30 ]. In our samples, near this cytogenetic location, deletions are affecting very few cases on both MF and LPP samples.…”

“…The last update was published by WHO-EORTC in 2018, and it comes with new histologic entities as a result of multiple molecular studies [ 8 ]. For a proper clinical approach of the patient, it is important to recognize these distinct forms of lymphoma based on morphology, immunophenotype, molecular and genetics of the disease [ 5 , 9 , 10 ].…”