Dataset Information

Recurrent Novel P2RY8/IGH Translocations in B-Lymphoblastic Leukemia/Lymphoma.

ABSTRACT: Translocations involving the immunoglobulin heavy chain (IGH) locus are common abnormalities in B-lymphoblastic leukemia/lymphoma (B-ALL) and multiple myeloma. These rearrangements result in a juxtaposition of IGH enhancers to the vicinity of oncogenes, such as MYC and CRLF2, leading to the upregulation of oncogenes. Here, we identified recurrent novel P2RY8/IGH translocations in three B-ALL patients by transcriptome sequencing. Noncoding exon 1 of P2RY8 was translocated to different sites of the IGH gene, resulting in transcripts of P2RY8/IGHM, P2RY8/IGHV, and P2RY8/IGHD. However, a high expression level of truncated P2RY8 was observed in the patients compared with healthy donors, which might be related to the aggressive clinical course and inferior outcome. In summary, we described recurrent novel P2RY8/IGH translocations with high expression levels of P2RY8, which may contribute to the guidelines for clinical diagnosis and treatment.

SUBMITTER: Fang Y

PROVIDER: S-EPMC9330356 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Recurrent Novel P2RY8/IGH Translocations in B-Lymphoblastic Leukemia/Lymphoma.

Fang Yanglan Y Wang Man M Hu Shuhong S Wang Tanzhen T Liu Yujie Y Xiao Jinyan J Cai Yiming Y Wang Ying Y Qiu Huiying H Tang Xiaowen X Chen Suning S Wu Depei D Xu Yang Y Liu Tianhui T

Frontiers in oncology 20220714

Translocations involving the immunoglobulin heavy chain (IGH) locus are common abnormalities in B-lymphoblastic leukemia/lymphoma (B-ALL) and multiple myeloma. These rearrangements result in a juxtaposition of IGH enhancers to the vicinity of oncogenes, such as MYC and CRLF2, leading to the upregulation of oncogenes. Here, we identified recurrent novel P2RY8/IGH translocations in three B-ALL patients by transcriptome sequencing. Noncoding exon 1 of P2RY8 ...[more]

PMID: 35912172

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Project description:Immunoglobulin heavy chain translocations (IGH-t) have occasionally been reported in Chinese patients with chronic lymphocytic leukemia (CLL). The objective of the present study was to identify the clinicopathologic features of patients with IGH-t CLL and compare them with those of patients with non-IGH-t CLL. We performed fluorescence in situ hybridization (FISH) based on a routine CLL prognostic FISH panel using IGH, IGH-BCL2, BCL3, IGH-CMYC, and BCL6 FISH probes. Furthermore, we retrospectively evaluated the clinical features of 138 newly diagnosed CLL patients via chromosome banding analysis (CBA), FISH, and targeted next-generation sequencing. IGH-t was identified in 25 patients (18.1%). Patients with IGH-t CLL had lower flow scores than those with non-IGH-t CLL. The most frequent translocation was t(14;18) (10 patients), followed by t(14;19) (3 patients), and t(2;14)(p13;q32), t(7;14)(q21.2;q12), t(9;14)(p13;q32) (3 patients). The remaining nine patients included three with abnormal karyotypes without translocation involving 14q32, four with a normal karyotype, and two who failed CBA. The most frequently concomitant FISH-detected aberrations were 13q deletion, followed by +12 and TP53 deletion, while one case involved ATM deletion. Complex karyotypes were detected in five patients with IGH-t CLL, in whom all partner genes were non-BCL2. Available mutational information indicated that KMT2D mutation was the most frequent mutation among tested 70 patients, while TP53 mutation was the most frequent mutation in the IGH-t group. Moreover, the IGH-t group had higher FBXW7 (P=0.014) and ATM (P=0.004) mutations than the non-IGH-t group, and this difference was statistically significant. Our study demonstrates that IGH-t is not uncommon among Chinese CLL patients, and that its partner genes are multiple. The gene mutational profile of the IGH-t group was distinct from that of the non-IGH-t group, and the concomitant chromosomal abnormalities within the IGH-t CLL group differed. Thus, identification of IGH-t and its partner genes in CLL patients may help further refine risk stratification and strengthen the accurate management in CLL patients.

Dataset Information

Recurrent Novel P2RY8/IGH Translocations in B-Lymphoblastic Leukemia/Lymphoma.

Publications

Recurrent Novel <i>P2RY8/IGH</i> Translocations in B-Lymphoblastic Leukemia/Lymphoma.

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