Myeloma Genetics and Genomics: Practice Implications and Future Directions

Faiman, Beth

doi:10.1016/j.clml.2014.07.008

Cited by 15 publications

(15 citation statements)

References 49 publications

(55 reference statements)

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“…Plasmacytoma develops later in the post-transplantation period. Although rare, PCN after KT occurs in younger patients compared to the general population, in which the median age of PCN at diagnosis is over 70 [5]. This may be mostly due to the fact that KT patients belong to a selected population, i.e., in France the median age is 55 years.…”

Section: Discussionmentioning

confidence: 99%

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Plasma cell neoplasia after kidney transplantation: French cohort series and review of the literature

et al. 2017

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Although post-transplant lymphoproliferative disorder (PTLD) is the second most common type of cancer in kidney transplantation (KT), plasma cell neoplasia (PCN) occurs only rarely after KT, and little is known about its characteristics and evolution. We included twenty-two cases of post-transplant PCN occurring between 1991 and 2013. These included 12 symptomatic multiple myeloma, eight indolent myeloma and two plasmacytomas. The median age at diagnosis was 56.5 years and the median onset after transplantation was 66.7 months (2–252). Four of the eight indolent myelomas evolved into symptomatic myeloma after a median time of 33 months (6–72). PCN-related kidney graft dysfunction was observed in nine patients, including six cast nephropathies, two light chain deposition disease and one amyloidosis. Serum creatinine was higher at the time of PCN diagnosis than before, increasing from 135.7 (±71.6) to 195.9 (±123.7) μmol/l (p = 0.008). Following transplantation, the annual rate of bacterial infections was significantly higher after the diagnosis of PCN, increasing from 0.16 (±0.37) to 1.09 (±1.30) (p = 0.0005). No difference was found regarding viral infections before and after PCN. Acute rejection risk was decreased after the diagnosis of PCN (36% before versus 0% after, p = 0.004), suggesting a decreased allogeneic response. Thirteen patients (59%) died, including twelve directly related to the hematologic disease. Median graft and patient survival was 31.7 and 49.4 months, respectively. PCN after KT occurs in younger patients compared to the general population, shares the same clinical characteristics, but is associated with frequent bacterial infections and relapses of the hematologic disease that severely impact the survival of grafts and patients.

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Section: Discussionmentioning

confidence: 99%

“…MM is consistently preceded by a pre-tumoral stage known as monoclonal gammopathy of undetermined significance (MGUS) [3,4]. After several chromosomal and genetic events, MGUS can move towards smoldering multiple myeloma (SMM), MM and eventually plasma cell leukemia [5,6]. …”

Section: Introductionmentioning

confidence: 99%

Plasma cell neoplasia after kidney transplantation: French cohort series and review of the literature

et al. 2017

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“…Today, whole genome/exome sequencing data of more than 300 MM patients are publically available from recent large sequencing studies [5–7, 3] describing genomic complexity of the disease including baseline clonal heterogeneity [4], linear and branching evolution [3], and therapeutic selection of clones and subclones resulting in clonal tides [2]. However, whereas genetic diagnostics in MM as cytogenetics, fluorescence-in-situ-hybridization and gene expression profiling are well established [8], individual mutation profiling has not yet been adopted to the routine risk assessment. In this work, we report on an innovative gene panel investigating 25 MM patients at sequential time points before and after therapy.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M3P)

et al. 2015

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Recent advances in genomic sequencing technologies now allow results from deep next-generation sequencing to be obtained within clinically meaningful timeframes, making this an attractive approach to better guide personalized treatment strategies. No multiple myeloma-specific gene panel has been established so far; we therefore designed a 47-gene-targeting gene panel, containing 39 genes known to be mutated in ≥3%of multiple myeloma cases and eight genes in pathways therapeutically targeted in multiple myeloma (MM). We performed targeted sequencing on tumor/germline DNA of 25 MM patients in which we also had a sequential sample post treatment. Mutation analysis revealed KRAS as the most commonly mutated gene (36 % in each time point), followed by NRAS (20 and 16 %), TP53 (16 and 16 %), DIS3 (16 and 16 %), FAM46C (12 and 16 %), and SP140 (12 and 12 %). We successfully tracked clonal evolution and identified mutation acquisition and/or loss in FAM46C, FAT1, KRAS, NRAS, SPEN, PRDM1, NEB, and TP53 as well as two mutations in XBP1, a gene associated with bortezomib resistance. Thus, we present the first longitudinal analysis of a MM-specific targeted sequencing gene panel that can be used for individual tumor characterization and for tracking clonal evolution over time.

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“…Using fluorescent in situ hybridization (FISH) and cytogenetics, approximately 50%-60% of MM cases have been identified as non-hyperdiploid and involving an early immunoglobulin heavy chain (IgH) translocation on chromosomes 4, 8, 11, and 16. 12 The remaining percentage of MM cases are characterized as hyperdiploid and most commonly affect chromosomes 3,5,7,9,11,15,19, and 21 as trisomies and chromosomes 13, 14, 16, and 22 as monosomies. Hyperdiploid MM is generally associated with a more favorable outcome.…”

Section: Background and Significancementioning

confidence: 99%

“…While research of the genomic components of MM has greatly contributed to the understanding of the MM pathogenesis, it has also revealed a further complexity of the disease. 7 Next-generation sequencing (NGS) has given researchers the ability to view hundreds of thousands of genetic variants in a single run. 8 The use of NGS in MM has made way for the discovery of many genomic variants specific to the disease but, similar to most genomic discoveries, has not made its way into evidence-based practice.…”

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confidence: 99%