Sylvain Mareschal, Ph.D.
Bioinformatics postdoc
May 4, 2017 at 19:48
Mareschal et al, JID 2017
J Invest Dermatol. 2017 May 4.
pii: S0022-202X(17)31429-X.
doi: 10.1016/j.jid.2017.04.010.
[Epub ahead of print]

Identification of somatic mutations in primary cutaneous diffuse large B-cell lymphoma, leg-type by massive parallel sequencing.

Mareschal S, Pham-Ledard A, Viailly PJ, Dubois S, Bertrand P, Maingonnat C, Fontanilles M, Bohers E, Ruminy P, Tournier I, Courville P, Lenormand B, Duval AB, Andrieu E, Verneuil L, Vergier B, Tilly H, Joly P, Frebourg T, Beylot-Barry M, Merlio JP, Jardin F.

To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma leg-type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma (DLBCL) subtypes, we analyzed a total cohort of 28 PCLBCL-LT cases by next generation sequencing with a Lymphopanel designed for DLBCL. We also analyzed 12 pairs of tumor and control DNA samples by whole exome sequencing which led us to perform resequencing of three selected genes not included in the Lymphopanel: TBL1XR1, KLHL6 and IKZF3. Our study clearly identifies an original mutational landscape of PCLBCL-LT with a very restricted set of highly recurrent mutations (>40%) involving MYD88 (p.L265P variant), PIM1 and CD79B. Other genes involved in B-cell signaling, NFKB activation or DNA modeling were found altered notably TBL1XR1 (33%), MYC (26%) CREBBP (26%) and IRF4 (21%) or HIST1H1E (41%). MYD88 L265P variant was associated with copy number variations or copy neutral loss of heterozygosity in 60% of cases. The most frequent genetic losses involved CDKN2A/2B, TNFAIP3/A20, PRDM1, TCF3 and CIITA. Altogether, these results show that PCLBCL-LT exhibits a unique mutational landscape combining highly recurrent hotspot mutations in genes involved in NF-kB and B-cell signaling pathways, which provides a rationale to use selective inhibitors of the B-cell receptor.

Pubmed, PMID: 28479318