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

AbstractThe 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 mutatedIGHV 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 genesFCRL1,FCRL2, andFCRL3 and in the lack of expression ofFCRL5, observed by RT-qPCR. The mutational status ofTP53,NOTCH1, SF3B1,MYD88,FBXW7, andXPO1 was investigated by targeted next-generation sequencing, detecting a frameshift deletion withinNOTCH1 (c.7544_7545delCT). We hypothesize a loss of tumor suppressor function forFCRL genes, cooperating withNOTCH1 mutation and 13q14 genomic loss in our patient, both conferring a negative prognosis, independently from the known biological prognostic factors of CLL.
Source: Clinical and Experimental Medicine - Category: Research Source Type: research