Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia

Poulain, Stéphanie; Roumier, Christophe; Galiègue‐Zouitina, Sylvie; Daudignon, Agnès; Herbaux, Charles; Aiijou, Rachid; Lainelle, Amélie; Broucqsault, Natacha; Bertrand, Elisabeth; Manier, Salomon; Renneville, Aline; Soenen, Valérie; Tricot, Sabine; Roche‐Lestienne, Catherine; Duthilleul, Patrick; Preudhomme, Claude; Quesnel, Bruno; Morel, Pierre; Leleu, Xavier

doi:10.1002/ajh.23545

Cited by 45 publications

(40 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High frequency of CD79A/CD79B mutation was also identified in PCNSL. Our current finding, that the MYD88 mutation was identified in the CSF of BNS without a BCR CD79-based activating mutation supports the concept that BNS might represent a pathogenetically distinct group of PCNSL (Montesinos-Rongen et al, 2011;Poulain et al, 2013b;Varettoni et al, 2013), and may help in the differential diagnosis as CD19 with K/L restriction is observed in the two diseases.…”

Section: Discussionsupporting

confidence: 66%

“…We have also reported these mutations in the bone marrow tumour cells of approximately 15% of WM patients (Poulain et al, 2013b). In parallel, mutations of CXCR4 were recently described in nearly 30% of WM.…”

Section: Absence Of Bcr Genes and Cxcr4 Mutationsmentioning

confidence: 69%

“…CN-LOH at 3p including MYD88 was observed in the second case, which harboured four additional CNA. CN-LOH targeting MYD88 is a recurrent but rare event and its prognostic value remains to be elucidated in WM (Poulain et al, 2013b;Hunter et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, DNA was analysed for the presence of the MYD88 L265P mutation with a commercially available assay that combines an allele-specific amplification with Amplification Refractory Mutation System (ARMS) technology and hydrolysis probe detection (Biomarker Somatic Mutation Assay, SABiosciences; Qiagen, Courtaboeuf, France) (qPCR), as previously described with slight modifications (Jimenez et al, 2013). We investigated the sensitivity of the method by analysing the DNA from a WM cell line characterized with the presence of MYD88 L265P (BCWM1) (data not shown) (Jimenez et al, 2013;Poulain et al, 2013b;Xu et al, 2013). CXCR4, CD79A and CD79B mutation were screened as previously described (Hunter et al, 2014).…”

Section: Flow Cytometrymentioning

confidence: 99%

See 3 more Smart Citations

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

et al. 2014

Self Cite

View full text Add to dashboard Cite

SummaryBing-Neel syndrome (BNS), a rare neurological syndrome associated with Waldenstr€ om macroglobulinaemia (WM), is a direct involvement of the central nervous system by lymphoplasmacytoid cells characterized with an adverse prognostic. The MYD88 L265P mutation has been identified in the vast majority of patients with WM. The diagnosis of BNS is often challenging because of the variety of clinical presentations associated with difficult histological techniques. We hypothesized that identification of MYD88 L265P mutation in the cerebrospinal fluid (CSF) would contribute to the diagnosis of BNS in addition to imaging, flow cytometry and cytology. We identified MYD88 L265P mutation in the CSF and the bone marrow of all cases of BNS using quantitative polymerase chain reaction qPCR and Sanger sequencing. Copy neutral loss of heterozygosity including MYD88 was observed in one case. No mutation of CXCR4, CD79A and CD79B was observed in parallel. We further showed that monitoring the quantitative expression of MYD88 L265P mutation might be a useful molecular tool to monitor response to chemotherapy using qPCR. In conclusion, identification of MYD88 L265P mutation might be a new molecular-based biomarker tool to add to the diagnostic and monitoring armamentarium for BNS.

show abstract

Section: Discussionsupporting

confidence: 66%

Section: Absence Of Bcr Genes and Cxcr4 Mutationsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

See 2 more Smart Citations

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…More than 90% a light-chain isotype-positive B cells was detected in all cases (mean, 95.8% of tumoral cells; ref. 15). …”

Section: Cell Selectionmentioning

confidence: 99%

Genomic Landscape of CXCR4 Mutations in Waldenström Macroglobulinemia

Poulain

Roumier

Venet-Caillault

et al. 2016

Clinical Cancer Research

Self Cite

104

View full text Add to dashboard Cite

Purpose: Whole-genome sequencing has revealed MYD88 L265P and CXCR4 mutations (CXCR4 mut ) as the most prevalent somatic mutations in Waldenstr€ om macroglobulinemia. CXCR4 mutation has proved to be of critical importance in Waldenstr€ om macroglobulinemia, in part due to its role as a mechanism of resistance to several agents. We have therefore sought to unravel the different aspects of CXCR4 mutations in Waldenstr€ om macroglobulinemia.Experimental Design: We have scanned the two coding exons of CXCR4 in Waldenstr€ om macroglobulinemia using deep nextgeneration sequencing and Sanger sequencing in 98 patients with Waldenstr€ om macroglobulinemia and correlated with SNP array landscape and mutational spectrum of eight candidate genes involved in TLR, RAS, and BCR pathway in an integrative study.Results: We found all mutations to be heterozygous, somatic, and located in the C-terminal domain of CXCR4 in 25% of the Waldenstr€ om macroglobulinemia. CXCR4 mutations led to a truncated receptor protein associated with a higher expression of CXCR4. CXCR4 mutations pertain to the same clone as to MYD88 L265P mutations but were mutually exclusive to CD79A/CD79B mutations (BCR pathway). We identified a genomic signature in CXCR4 mut Waldenstr€ om macroglobulinemia traducing a more complex genome. CXCR4 mutations were also associated with gain of chromosome 4, gain of Xq, and deletion 6q.Conclusions: Our study panned out new CXCR4 mutations in Waldenstr€ om macroglobulinemia and identified a specific signature associated to CXCR4 mut , characterized with complex genomic aberrations among MYD88L265P Waldenstr€ om macroglobulinemia. Our results suggest the existence of various genomic subgroups in Waldenstr€ om macroglobulinemia.

show abstract

Lymphoproliferative Disorders

Alper¹

2019

Bone Marrow Pathology

View full text Add to dashboard Cite

Background and Objectives. Trisomy 12 is one of the most common chromosomal abnormalities in B-cell chronic lymphocytic leukemia (CLL). The aberration is readily detected by fluorescence in situ hybridization (FISH). There are only a few reports in which FISH analyses have been used to study the expansion of the trisomy 12 clone over time.Design and Methods. Repeat FISH analyses were performed in 77 patients with a chronic leukemic B-cell disorder. The aim was to study the development of the trisomy 12 clone throughout the course of the disease, to measure the effect of therapy on the proportion of trisomic cells, and to relate the findings to the response to therapy.Results. Fifty-eight of the 60 patients with no trisomy 12 at the initial test were consistently disomic for chromosome 12, while 2 patients seemingly acquired trisomy 12 during follow-up. Seventeen patients showed trisomy 12 at the first test. Expansion of the trisomy 12 clone was seen in all patients with a progressive lymphocytosis. In contrast to poor responders, patients responding well to chemotherapy showed a significant decrease in the proportion of CD19 + cells with trisomy 12. The effect of purine analogs in patients with trisomy 12 seemed inferior, both clinically and when studying the effect on the trisomic clone. Interpretations and Conclusions.There is a strong association between expansion of the trisomy 12 clone and progressive disease, both in treated and untreated patients. Conversely, reduction of the trisomic B-cell clone was linked to clinical response to chemotherapy. Acquisition of trisomy 12 remains a rare event. ©2001, Ferrata Storti FoundationKey words: chronic leukemic B-cell disorders, CLL, trisomy 12, APAAP-FISH, treatment. © F e r r a t a S t o r t i F o u n d a t i o n © F e r r a t a S t o r t i F o u n d a t i o n © F e r r a t a S t o r t i F o u n d a t i o n

show abstract

Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia

Cited by 45 publications

References 34 publications

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

Genomic Landscape of CXCR4 Mutations in Waldenström Macroglobulinemia

Lymphoproliferative Disorders

Contact Info

Product

Resources

About