UAMS Smoldering Myeloma Myeloma Sequencing

Identifying high risk smoldering myeloma patients and progression mechanism is a prerequisite to implement effective inception strategies and curve myeloma related morbidity and mortality. We hypothesize that genomics may help identify determinants of progression that may help predict outcome and offer effective chemo preventive targets. Eighty-two patients underwent a custom targeted panel sequencing with an additional capture for the translocation loci. These results were compared to 223 newly diagnosed patients (EGAS00001003223 and EGAD00001004117) and 17 MGUS and 10 early myeloma patients. DNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems). After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads. Overall, these data highlight the importance of dysregulation of the MAPK pathway in the progression to MM.

Type: Other
Archiver: EGA European Genome-Phenome Archive

1 Dataset 2 Publications

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Dataset ID	Description	Technology	Samples
EGAD00001005285	Identifying high risk smoldering myeloma patients and progression mechanism is a prerequisite to implement effective inception strategies and curve myeloma related morbidity and mortality. We hypothesize that genomics may help identify determinants of progression that may help predict outcome and offer effective chemo preventive targets. Eighty-two patients underwent a custom targeted panel sequencing with an additional capture for the translocation loci. These results were compared to 223 newly diagnosed patients (EGAS00001003223 and EGAD00001004117) and 17 MGUS and 10 early myeloma patients. DNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems). After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads. Overall, these data highlight the importance of dysregulation of the MAPK pathway in the progression to MM.	NextSeq 500	241

Publications	Citations
The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma. Boyle EM, Deshpande S, Tytarenko R, Ashby C, Wang Y, Bauer MA, Johnson SK, Wardell CP, Thanendrarajan S, Zangari M, Facon T, Dumontet C, Barlogie B, Arbini A, Rustad EH, Maura F, Landgren O, Zhan F, van Rhee F, Schinke C, Davies FE, Morgan GJ, Walker BA. Nat Commun 12: 2021 293	33
Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes. Bustoros M, Anand S, Sklavenitis-Pistofidis R, Redd R, Boyle EM, Zhitomirsky B, Dunford AJ, Tai YT, Chavda SJ, Boehner C, Neuse CJ, Rahmat M, Dutta A, Casneuf T, Verona R, Kastritis E, Trippa L, Stewart C, Walker BA, Davies FE, Dimopoulos MA, Bergsagel PL, Yong K, Morgan GJ, Aguet F, Getz G, Ghobrial IM. Nat Commun 13: 2022 3449	5

Publications

Citations

The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma.
Boyle EM, Deshpande S, Tytarenko R, Ashby C, Wang Y, Bauer MA, Johnson SK, Wardell CP, Thanendrarajan S, Zangari M, Facon T, Dumontet C, Barlogie B, Arbini A, Rustad EH, Maura F, Landgren O, Zhan F, van Rhee F, Schinke C, Davies FE, Morgan GJ, Walker BA. Nat Commun 12: 2021 293

Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes.
Bustoros M, Anand S, Sklavenitis-Pistofidis R, Redd R, Boyle EM, Zhitomirsky B, Dunford AJ, Tai YT, Chavda SJ, Boehner C, Neuse CJ, Rahmat M, Dutta A, Casneuf T, Verona R, Kastritis E, Trippa L, Stewart C, Walker BA, Davies FE, Dimopoulos MA, Bergsagel PL, Yong K, Morgan GJ, Aguet F, Getz G, Ghobrial IM. Nat Commun 13: 2022 3449