Premium
Genomic analysis reveals recurrent deletion of JAK‐STAT signaling inhibitors HNRNPK and SOCS1 in mycosis fungoides
Author(s) -
Bastidas Torres Armando N.,
Cats Davy,
Mei Hailiang,
Szuhai Karoly,
Willemze Rein,
Vermeer Maarten H.,
Tensen Cornelis P.
Publication year - 2018
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22679
Subject(s) - biology , cdkn2a , mycosis fungoides , genetics , gene , cancer research , adapter molecule crk , carcinogenesis , cdkn2b , lymphoma , immunology , signal transducing adaptor protein
Mycosis fungoides (MF) is the most common cutaneous T‐cell lymphoma (CTCL). Causative genetic alterations in MF are unknown. The low recurrence of pathogenic small‐scale mutations (ie, nucleotide substitutions, indels) in the disease, calls for the study of additional aspects of MF genetics. Here, we investigated structural genomic alterations in tumor‐stage MF by integrating whole‐genome sequencing and RNA‐sequencing. Multiple genes with roles in cell physiology ( n = 113) and metabolism ( n = 92) were found to be impacted by genomic rearrangements, including 47 genes currently implicated in cancer. Fusion transcripts involving genes of interest such as DOT1L , KDM6A , LIFR , TP53 , and TP63 were also observed. Additionally, we identified recurrent deletions of genes involved in cell cycle control, chromatin regulation, the JAK‐STAT pathway, and the PI‐3‐K pathway. Remarkably, many of these deletions result from genomic rearrangements. Deletion of tumor suppressors HNRNPK and SOCS1 were the most frequent genetic alterations in MF after deletion of CDKN2A . Notably, SOCS1 deletion could be detected in early‐stage MF. In agreement with the observed genomic alterations, transcriptome analysis revealed up‐regulation of the cell cycle, JAK‐STAT, PI‐3‐K and developmental pathways. Our results position inactivation of HNRNPK and SOCS1 as potential driver events in MF development.