The spectrum of somatic mutations in monoclonal gammopathy of
undetermined significance indicates a less complex genomic
landscape than that in multiple myeloma

J 2017

The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma

MIKULÁŠOVÁ, Aneta, Christopher P. WARDELL, Alexander MURISON, Eileen M. BOYLE, Graham H. JACKSON et. al.

Basic information

Original name

The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma

Authors

MIKULÁŠOVÁ, Aneta (203 Czech Republic, belonging to the institution), Christopher P. WARDELL (840 United States of America), Alexander MURISON (826 United Kingdom of Great Britain and Northern Ireland), Eileen M. BOYLE (826 United Kingdom of Great Britain and Northern Ireland), Graham H. JACKSON (826 United Kingdom of Great Britain and Northern Ireland), Jan SMETANA (203 Czech Republic, belonging to the institution), Zuzana KUFOVA (203 Czech Republic), Luděk POUR (203 Czech Republic), Viera SANDECKÁ (703 Slovakia), Martina ALMÁŠI (203 Czech Republic), Pavla VŠIANSKÁ (203 Czech Republic), Evzen GREGORA (203 Czech Republic), Petr KUGLÍK (203 Czech Republic, belonging to the institution), Roman HÁJEK (203 Czech Republic), Faith E. DAVIES (840 United States of America), Gareth J. MORGAN (840 United States of America) and Brian A. WALKER (840 United States of America)

Edition

Haematologica, Pavia, Ferrata Storti Foundation, 2017, 0390-6078

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 9.090

RIV identification code

RIV/00216224:14310/17:00095684

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3324/haematol.2017.163766

UT WoS

000408743300030

Keywords in English

Monoclonal gammopathy

Abstract

V originále

Monoclonal gammopathy of undetermined significance is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little is known about the molecular mechanism of malignant transformation. We performed whole exome sequencing together with comparative genomic hybridization plus single nucleotide polymorphism array analysis in 33 flow-cytometry-separated abnormal plasma cell samples from patients with monoclonal gammopathy of undetermined significance to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in monoclonal gammopathy of undetermined significance than in myeloma (P<10-4) and we identified six genes that were significantly mutated in myeloma (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) within the monoclonal gammopathy of undetermined significance dataset. We also found a positive correlation with increasing chromosome changes and somatic gene mutations. IGH translocations, comprising t(4;14), t(11;14), t(14;16) and t(14;20), were present in 27.3% of cases and in a similar frequency to myeloma, consistent with the primary lesion hypothesis. MYC translocations and TP53 deletions or mutations were not detected in samples from patients with monoclonal gammopathy of undetermined significance, indicating that they may be drivers of progression to myeloma. Data from this study show that monoclonal gammopathy of undetermined significance is genetically similar to myeloma, however overall genetic abnormalities are present at significantly lower levels in monoclonal gammopathy of undetermined significant than in myeloma.

Links

NT13492, research and development project

Name: Úloha genetických abnormalit ve vývoji a progresi prekancerózy monoklonální gamapatie nejasného významu

Citovat

MIKULÁŠOVÁ, Aneta, Christopher P. WARDELL, Alexander MURISON, Eileen M. BOYLE, Graham H. JACKSON, Jan SMETANA, Zuzana KUFOVA, Luděk POUR, Viera SANDECKÁ, Martina ALMÁŠI, Pavla VŠIANSKÁ, Evzen GREGORA, Petr KUGLÍK, Roman HÁJEK, Faith E. DAVIES, Gareth J. MORGAN and Brian A. WALKER. The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma. Haematologica. Pavia: Ferrata Storti Foundation, 2017, vol. 102, No 9, p. 1617-1625. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2017.163766.

@article{1399950,
   author = {Mikulášová, Aneta and Wardell, Christopher P. and Murison, Alexander and Boyle, Eileen M. and Jackson, Graham H. and Smetana, Jan and Kufova, Zuzana and Pour, Luděk and Sandecká, Viera and Almáši, Martina and Všianská, Pavla and Gregora, Evzen and Kuglík, Petr and Hájek, Roman and Davies, Faith E. and Morgan, Gareth J. and Walker, Brian A.},
   article_location = {Pavia},
   article_number = {9},
   doi = {http://dx.doi.org/10.3324/haematol.2017.163766},
   keywords = {Monoclonal gammopathy},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma},
   volume = {102},
   year = {2017}
}

TY  - JOUR
ID  - 1399950
AU  - Mikulášová, Aneta - Wardell, Christopher P. - Murison, Alexander - Boyle, Eileen M. - Jackson, Graham H. - Smetana, Jan - Kufova, Zuzana - Pour, Luděk - Sandecká, Viera - Almáši, Martina - Všianská, Pavla - Gregora, Evzen - Kuglík, Petr - Hájek, Roman - Davies, Faith E. - Morgan, Gareth J. - Walker, Brian A.
PY  - 2017
TI  - The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma
JF  - Haematologica
VL  - 102
IS  - 9
SP  - 1617-1625
EP  - 1617-1625
PB  - Ferrata Storti Foundation
SN  - 03906078
KW  - Monoclonal gammopathy
N2  - Monoclonal gammopathy of undetermined significance is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little is known about the molecular mechanism of malignant transformation. We performed whole exome sequencing together with comparative genomic hybridization plus single nucleotide polymorphism array analysis in 33 flow-cytometry-separated abnormal plasma cell samples from patients with monoclonal gammopathy of undetermined significance to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in monoclonal gammopathy of undetermined significance than in myeloma (P<10-4) and we identified six genes that were significantly mutated in myeloma (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) within the monoclonal gammopathy of undetermined significance dataset. We also found a positive correlation with increasing chromosome changes and somatic gene mutations. IGH translocations, comprising t(4;14), t(11;14), t(14;16) and t(14;20), were present in 27.3% of cases and in a similar frequency to myeloma, consistent with the primary lesion hypothesis. MYC translocations and TP53 deletions or mutations were not detected in samples from patients with monoclonal gammopathy of undetermined significance, indicating that they may be drivers of progression to myeloma. Data from this study show that monoclonal gammopathy of undetermined significance is genetically similar to myeloma, however overall genetic abnormalities are present at significantly lower levels in monoclonal gammopathy of undetermined significant than in myeloma.
ER  -

MIKULÁŠOVÁ, Aneta, Christopher P. WARDELL, Alexander MURISON, Eileen M. BOYLE, Graham H. JACKSON, Jan SMETANA, Zuzana KUFOVA, Luděk POUR, Viera SANDECKÁ, Martina ALMÁŠI, Pavla VŠIANSKÁ, Evzen GREGORA, Petr KUGLÍK, Roman HÁJEK, Faith E. DAVIES, Gareth J. MORGAN and Brian A. WALKER. The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma. \textit{Haematologica}. Pavia: Ferrata Storti Foundation, 2017, vol.~102, No~9, p.~1617-1625. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2017.163766.

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