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

Giulia Daniele, Alberto L’Abbate, Antonella Turchiano, Orazio Palumbo, Massimo Carella, Crocifissa Lo Cunsolo, Paolo Iuzzolino, Angelo Lonoce, María Hernández-Sánchez, Carla Minoia, Patrizia Leone, Jesus Maria Hernandez-Rivas, Clelia Tiziana Storlazzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalClinical and Experimental Medicine
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Fc Receptors
B-Cell Chronic Lymphocytic Leukemia
Down-Regulation
Genes
Chromosomes, Human, Pair 1
Chromosomes
RNA Sequence Analysis
Chromosome Deletion
Hematologic Diseases
Biological Factors
Single Nucleotide Polymorphism
Tumors
Genome
RNA
Derivatives
Mutation
Neoplasms
Therapeutics

Keywords

  • 1q23.1 deletion
  • CLL
  • FCRL
  • IGHV
  • NOTCH1
  • Translocation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia. / Daniele, Giulia; L’Abbate, Alberto; Turchiano, Antonella; Palumbo, Orazio; Carella, Massimo; Lo Cunsolo, Crocifissa; Iuzzolino, Paolo; Lonoce, Angelo; Hernández-Sánchez, María; Minoia, Carla; Leone, Patrizia; Hernandez-Rivas, Jesus Maria; Storlazzi, Clelia Tiziana.

In: Clinical and Experimental Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Daniele, Giulia ; L’Abbate, Alberto ; Turchiano, Antonella ; Palumbo, Orazio ; Carella, Massimo ; Lo Cunsolo, Crocifissa ; Iuzzolino, Paolo ; Lonoce, Angelo ; Hernández-Sánchez, María ; Minoia, Carla ; Leone, Patrizia ; Hernandez-Rivas, Jesus Maria ; Storlazzi, Clelia Tiziana. / 1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia. In: Clinical and Experimental Medicine. 2019.
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AU - Daniele, Giulia

AU - L’Abbate, Alberto

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AU - Palumbo, Orazio

AU - Carella, Massimo

AU - Lo Cunsolo, Crocifissa

AU - Iuzzolino, Paolo

AU - Lonoce, Angelo

AU - Hernández-Sánchez, María

AU - Minoia, Carla

AU - Leone, Patrizia

AU - Hernandez-Rivas, Jesus Maria

AU - Storlazzi, Clelia Tiziana

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N2 - 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.

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.

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