Detection of activating<i>MAP2K1</i>mutations in atypical hairy cell leukemia and hairy cell leukemia variant

Mason, Emily F.; Szeto, David; Gibson, Christopher J.; Jia, Yonghui; Garcia, Elizabeth; Jacobson, Caron A.; Cin, Paola Dal; Kuo, Frank C.; Pinkus, Geraldine S.; Lindeman, Neal I.; Sholl, Lynette M.; Aster, Jon C.; Morgan, Elizabeth A.

doi:10.1080/10428194.2016.1185786

Cited by 43 publications

(36 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, this initiative has enabled a large number of other more focused studies of common and uncommon tumor types and, in particular, has permitted prospective identification of relatively uncommon genomic variants to facilitate clinical trial enrollment and biomarker studies (46)(47)(48)(49)(50)(51)(52)(53)(54). Migrating to a clinical test, identifying when in the course of a patient's disease genomic profiling should be used, and triaging patients in real-time for clinical trial enrollment should contribute to determining clinical utility on a broader scale.…”

Section: Discussionmentioning

confidence: 99%

Institutional implementation of clinical tumor profiling on an unselected cancer population

Sholl¹,

Khanh²,

Shivdasani³

et al. 2016

JCI Insight

Self Cite

355

314

View full text Add to dashboard Cite

BACKGROUND.Comprehensive genomic profiling of a patient's cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprisewide, unselected cancer patient population has yet to be reported. METHODS.We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested.RESULTS. Our cohort consists of cancer patients unrestricted by disease site or stage. Across all consented patients, half had sufficient and available (>20% tumor) material for profiling; once specimens were received in the laboratory for pathology review, 73% were scored as adequate for genomic testing. When sufficient DNA was obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an actionable or informative alteration; only 19% of these represented a current standard of care for therapeutic stratification. The findings recapitulate those of previous studies of common cancers but also identify alterations, including in AXL and EGFR, associated with response to targeted therapies. In rare cancers, potentially actionable alterations suggest the utility of a "cancer-agnostic" approach in genomic profiling. Retrospective analyses uncovered contextual genomic features that may inform therapeutic response and examples where diagnoses revised by genomic profiling markedly changed clinical management. CONCLUSIONS.Broad sequencing-based testing deployed across an unselected cancer cohort is feasible. Genomic results may alter management in diverse scenarios; however, additional barriers must be overcome to enable precision cancer medicine on a large scale.

show abstract

Section: Discussionmentioning

confidence: 99%

Institutional implementation of clinical tumor profiling on an unselected cancer population

Sholl¹,

Khanh²,

Shivdasani³

et al. 2016

JCI Insight

Self Cite

355

314

View full text Add to dashboard Cite

show abstract

“…BRAF V600E mutations are found in almost all cases of hairy cell leukemia (HCL) but not in HCL-variant (HCL-v) or other small B-cell lymphoid neoplasms [49-52]. Mutations in MAP2K1 which encodes MEK1 (which is downstream of BRAF) have been reported in almost half of HCL-v and in the majority of HCL that use IGHV4-34 and which, like HCL-v, lack BRAF V600E mutations [53,54]. MYD88 mutation is important in the differential diagnosis between nodal marginal zone lymphoma and lymphoplasmacytic lymphoma (LPL) [55-58].…”

Section: Molecular Testing Using Next-generation Sequencing: Future Nmentioning

confidence: 99%

Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives

Jeon

Yoon

Paik

et al. 2017

J Pathol Transl Med

View full text Add to dashboard Cite

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

show abstract

“…The genomic data are consistent with this observation because, although the genomic abnormalities in CBL-MZ overlap with those found in any of the well-defined entities into which it could evolve, the incidence of mutations is lower and does not mirror any specific disease. However, important caveats are the relatively small number of cases in the current study and the lack of concordance among genomic studies in other rare disorders, such as HCL-v 19 and SDRPL. 11,20,21 Further larger studies, ideally including immunogenetic, whole genomic sequencing, and epigenetic data, will be required to confirm the relationship between CBL-MZ and established WHO disorders and to identify additional drivers of progressive disease.…”

mentioning

confidence: 99%

CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

et al. 2018

View full text Add to dashboard Cite

The term "clonal B cell lymphocytosis of marginal zone origin" (CBL-MZ) 1,2 has recently been suggested for asymptomatic individuals whose routine blood count shows a persistent modest lymphocytosis that is usually accompanied by bone marrow involvement. This immunophenotype is suggestive of marginal zone/postgerminal center derivation, but no other features of a chronic B cell lymphoproliferative disorder are found, other than a low-level paraprotein in some cases. Cases with a clonal lymphocyte count ,5 3 10 9 /L would fall within the revised World Health Organization (WHO) category of non-chronic lymphocytic leukemia-type monoclonal B-cell lymphocytosis. In 3 previous series of CBL-MZ consisting of 102, 53, and 16 cases with median follow-ups (FUs) of 60, 34, and 44 months, respectively, 1,3,4 the overall incidence of progression was 15.7%, with the majority (11.1%) developing splenomegaly that frequently did not require treatment. However, it remains unclear whether CBL-MZ is the precursor to 1 or several well-defined WHO entities and what factors predict disease progression. To address this, we performed a genomic analysis of a well-characterized cohort of CBL-MZ cases with long FU and provide evidence to show that CBL-MZ is not a single biological entity.This study includes data from 37 patients with CBL-MZ diagnosed and managed at the Royal Bournemouth Hospital. Clinical, routine laboratory, morphological, immunophenotypic, immunogenetic, and cytogenetic data have been reported on 36 cases using previously described methods.

show abstract

Detection of activatingMAP2K1mutations in atypical hairy cell leukemia and hairy cell leukemia variant

Cited by 43 publications

References 15 publications

Institutional implementation of clinical tumor profiling on an unselected cancer population

Institutional implementation of clinical tumor profiling on an unselected cancer population

Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives

CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

Contact Info

Product

Resources

About