GRCh38 · COSMIC v92

Overview

This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53.
Paper ID
COSP47139
Authors
Chapiro E, Pramil E, Diop M, Roos-Weil D, Dillard C, Gabillaud C, Maloum K, Settegrana C, Baseggio L, Lesesve JF, Yon M, Jondreville L, Lesty C, Davi FB, Le Garff-Tavernier M, Droin NM, Dessen P, Algrin C, Leblond V, Gabarre J, Bouzy S, Eclache V, Gaillard B, Callet-Bauchu E, Muller M, Lefebvre C, Nadal N, Ittel A, Struski S, Collonge-Rame MA, Quilichini B, Fert-Ferrer S, Auger N, Radford-Weiss I, Wagner L, Scheinost S, Zenz T, Susin SA, Bernard OA and Nguyen-Khac F
Affiliation
AP-HP, France.
Journal
Blood, 2019
ISSN: 1528-0020
PMID: 31527074 (view at PubMed or Europe PMC)
Abstract
B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessment of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex ({greater than or equal to}3 abnormalities) in 73% of the patients and highly complex (<u>&gt;</u>5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving <i>MYC</i> [t(<i>MYC</i>)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six of the 34 patients (76%) exhibit <i>MYC</i> aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in <i>TP53</i>, <i>MYD88</i>, <i>BCOR</i>, <i>MYC</i>, <i>SF3B1</i>, <i>SETD2</i>, <i>CHD2</i>, <i>CXCR4</i>, and <i>BCLAF1</i> The majority of B-PLL used the <i>IGHV3</i> or <i>IGHV4</i> subgroups (89%), and displayed significantly mutated <i>IGHV</i> genes (79%). We identified three distinct cytogenetic risk groups: low-risk (no <i>MYC</i> aberration), intermediate-risk (<i>MYC</i> aberration but no del17p), and high-risk (<i>MYC</i> aberration and del17p) (p=.0006). <i>In vitro</i> drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif (BET) inhibitor targeting <i>MYC</i>) was associated with significantly lower viability of B-PLL cells harboring a t(<i>MYC</i>). We conclude that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting <i>MYC</i> may be a useful treatment option in this disease.
Paper Status
Curated
Genes Analysed
1012
Mutated Samples
16
Total No. of Samples
16

Mutation Matrix

This section shows the correlation plot between the top 20 genes and samples. There is more information in our help pages.

Genes

This table shows genes with mutations in the selected study/paper [more details]
Genes Mutated Samples
This table shows genes without mutations in the selected study/paper [more details]

Table Information

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This is a whole exome/systematic screen paper and the negatives for this paper should be inferred.

Variants

This tab shows genes with mutations in the selected study/paper [more details]

Genes Samples CDS Mutation AA Mutation

This tab shows non coding variant in the selected study/paper [more details]

Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq FATHMM-MKL

This tab shows the gene expression and copy number variation data for this study [more details]

Table Information

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The table currently shows only high value (numeric) copy number data. Copy number segments are excluded if the total copy number and minor allele values are unknown.

Click here to include all copy number data. For more detailed information about copy number data and gain/loss definitions click here.

Sample Gene Expression Expr Level (Z-Score)

Over Expressed; Z-Score > 2.0

Under Expressed; Z-Score < -2.0

Normal; Z-Score within the range -2.0 to 2.0

CN Type Minor Allele Copy Number CN Segment Posn. Average Ploidy

1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy.

3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.

CNV

This table lists the samples in the selected study which have low/high methylation for each gene. [more details]

No data

This tab shows the fusion mutations observed in this sample [more details]

Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type

Samples

This table shows mutated samples in the selected study/paper.

Sample Name Mutation Count

This table shows samples without mutations in the selected study/paper.

Non-Mutant Samples Sample Id (COSS)