The research team led by Prof. Francesco Bertoni has recently added information on our knowledge of two hematological malignancies: MALT Lymphoma and Peripheral T-cell lymphoma. The results have been published in Haematologica and Modern Pathology, respectively.
Using high-throughput sequencing techniques (DNA copy number analysis, targeted DNA sequencing, DNA methylation and RNA-sequencing), Dr Luciano Cascione, Dr Andrea Rinaldi and Collaborators have shown how MALT lymphoma is characterized by frequent lesions affecting chromatin remodeling, BCR/Nf-kB and NOTCH pathways (TNFAIP3, KMT2C, TET2 and NOTCH1/2), besides trisomies of chromosomes 3 and 18. Lymphomas from different anatomic sites exhibit a different spectrum of genetic lesions, with a particular high frequency of TET2 in thyroid lesions. TET2 mutations are also associated with a specific methylation signature. The observed landscape, alongside transcriptome data, suggests the exploration of epigenetics drugs therapy in at least a subgroup of MALT lymphoma patients.
In the second paper, Dr Antonella Laginestra from Prof. Stefano Pileri’s team, Dr Luciano Cascione and Collaborators have applied whole exome sequencing and RNA-sequencing to study the genetics of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). In addition to epigenetic modifiers implicated in all subtypes of T-cell neoplasm (TET2, DNMT3A, KMT2D, KMT2C, SETD2), recurrent mutations of the FAT1 tumor suppressor gene were for the first time recorded in 39% of cases along with mutations of other tumor suppressor genes (LATS1, STK3, ATM, TP53, TP63). Patients with FAT1 mutations showed inferior overall survival compared to those with wild-type version, highlighting how FAT1 plays a pathogenetic and prognostic role in this neoplasm.
Both works were possible thanks to international collaborations and have their results are publicly available.
Cascione L, Rinaldi A, Bruscaggin A, Tarantelli C, Arribas AJ, Kwee I,
Pecciarini L, Mensah AA, Spina V, Chung EYL, Terzi di Bergamo L, Dirnhofer S,
Tzankov A, Miranda RN, Young KH, Traverse-Glehen A, Gaidano G, Swerdlow SH,
Gascoyne R, Rabadan R, Ponzoni M, Bhagat G, Rossi D, Zucca E, Bertoni F.
Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next
generation sequencing analyses.
Haematologica. 2019 Apr 24. pii: haematol.2018.214957. doi: 10.3324/haematol.2018.214957. PubMed PMID: 31018978.
Laginestra MA, Cascione L, Motta G, Fuligni F, Agostinelli C, Rossi M,
Sapienza MR, Righi S, Broccoli A, Indio V, Melle F, Tabanelli V, Calleri A,
Novero D, Facchetti F, Inghirami G, Sabattini E, Bertoni F, Pileri SA.
Wholeexome sequencing reveals mutations in FAT1 tumor suppressor gene clinically
impacting on peripheral T-cell lymphoma not otherwise specified.
Mod Pathol. 2019 Apr 25. doi: 10.1038/s41379-019-0279-8. PubMed PMID:31028364.