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
Gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent in breast implant-associated ALCL.
Paper ID
COSP47421
Authors
Laurent C, Nicolae A, Laurent C, Le Bras F, Haioun C, Fataccioli V, Amara N, Adélaïde J, Guille A, Schiano JM, Tesson B, Traverse-Glehen A, Chenard MP, Mescam L, Moreau A, Chassagne-Clement C, Somja J, Escudié F, André M, Martin N, Lacroix L, Lemonnier F, Hamy-Petit AS, Reyal F, Bannier M, Oberic L, Prade N, Frénois FX, Beldi-Ferchiou A, Delfau-Larue MH, Bouabdallah R, Birnbaum D, Brousset P, Xerri L and Gaulard P
Affiliation
CHU Toulouse, IUCT Oncopole, Centre de Recherche en Cancerologie de Toulouse Inserm UMR 1037,, Toulouse, France.
Journal
Blood, 2019
ISSN: 1528-0020
PMID: 31774495 (view at PubMed or Europe PMC)
Abstract
The oncogenic events involved in breast implant-associated anaplastic large cell lymphoma (BI-ALCL) remain elusive. To clarify this point, we have characterized the genomic landscape of 34 BI-ALCLs (15 tumor, 19 in situ subtypes) collected from 54 BI-ALCL patients diagnosed through the French Lymphopath network. Whole exome sequencing (n=22, with paired tumor/germline DNA) and/or targeted deep sequencing (n=24) showed recurrent mutations of epigenetic modifiers in 74% of cases, involving notably KMT2C (26%), KMT2D (9%), CHD2 (15%) and CREBBP (15%). KMT2D and KMT2C mutations correlated with a loss of H3K4 mono- and tri-methylation by immunohistochemistry. Twenty cases (59%) showed mutations in at least one member of the JAK/STAT pathway including STAT3 (38%), JAK1 (18%), STAT5B (3%) and in negative regulators like SOCS3 (6%), SOCS1 (3%) and PTPN1 (3%). These mutations were more frequent in tumor-type than in situ samples (p=0.038). All BI-ALCLs expressed pSTAT3, regardless of the mutational status of genes in JAK/STAT pathway. Mutations in EOMES gene (12%) involved in lymphocytes development, PI3K-AKT/mTOR (6%) and loss of function mutations in TP53 (12%) were also identified. Copy number aberration (CNA) analysis identified recurrent alterations including gains on chromosomes 2, 9p, 12p and 21 and losses on 4q, 8p, 15, 16 and 20. Regions of CNA encompassed genes involved in JAK/STAT pathway and epigenetic regulators. Our results show that BI-ALCL genomic landscape is not only characterized by JAK/STAT activating mutations but also loss-of-function alterations of epigenetic modifiers.
Paper Status
Curated
Genes Analysed
4150
Mutated Samples
34
Total No. of Samples
34

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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The negatives shown on this page are only from targeted gene screens, but does not include negatives from whole exome/systematic screens( these negatives should be inferred ).

Non-Mutant Genes Gene Id (COSG)

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)