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1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia.

Abstract：

:The identification of chromosome 1 translocations and deletions is a rare and poorly investigated event in chronic lymphocytic leukemia (CLL). Nevertheless, the identification of novel additional molecular alterations is of great interest, opening to new prognostic and therapeutic strategies for such heterogeneous hematological disease. We here describe a patient affected by CLL with a mutated IGHV status, showing a balanced t(1;3)(q23.1;q21.3) translocation and a der(18)t(1;18)(q24.2;p11.32), accompanying the recurrent 13q14 heterozygous deletion in all analyzed cells at onset. By combining whole-genome sequencing, SNP array, RNA sequencing, and FISH analyses, we defined a 1q23.1 biallelic minimally deleted region flanking translocations breakpoints at both derivative chromosome 1 homologues. The deletion resulted in the downregulation of the Fc receptor-like family genes FCRL1, FCRL2, and FCRL3 and in the lack of expression of FCRL5, observed by RT-qPCR. The mutational status of TP53, NOTCH1, SF3B1, MYD88, FBXW7, and XPO1 was investigated by targeted next-generation sequencing, detecting a frameshift deletion within NOTCH1 (c.7544_7545delCT). We hypothesize a loss of tumor suppressor function for FCRL genes, cooperating with NOTCH1 mutation and 13q14 genomic loss in our patient, both conferring a negative prognosis, independently from the known biological prognostic factors of CLL.

journal_name

Clin Exp Med

journal_title

Clinical and experimental medicine

authors

Daniele G,L'Abbate A,Turchiano A,Palumbo O,Carella M,Lo Cunsolo C,Iuzzolino P,Lonoce A,Hernández-Sánchez M,Minoia C,Leone P,Hernandez-Rivas JM,Storlazzi CT

doi

10.1007/s10238-019-00551-0

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

261-267

issue

2

eissn

1591-8890

issn

1591-9528

pii

10.1007/s10238-019-00551-0

journal_volume

19

pub_type

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