TY - JOUR
AU1 - Daniele, Giulia
AU2 - L’Abbate, Alberto
AU3 - Turchiano, Antonella
AU4 - Palumbo, Orazio
AU5 - Carella, Massimo
AU6 - Lo Cunsolo, Crocifissa
AU7 - Iuzzolino, Paolo
AU8 - Lonoce, Angelo
AU9 - Hernández-Sánchez, María
AU1 - Minoia, Carla
AU1 - Leone, Patrizia
AU1 - Hernandez-Rivas, Jesus
AU1 - Storlazzi, Clelia
AB - 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.
TI - 1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia
JF - Clinical and Experimental Medicine
DO - 10.1007/s10238-019-00551-0
DA - 2019-03-15
UR - https://www.deepdyve.com/lp/springer-journals/1q23-1-homozygous-deletion-and-downregulation-of-fc-receptor-like-eaKCQ20NHX
SP - 261
EP - 267
VL - 19
IS - 2
DP - DeepDyve
ER -