Complex patterns of chromosome 11 aberrations in myeloid
malignancies target CBL, MLL, DDB1 and LMO2

J 2013

Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2

KLAMPFL, T., J. MILOSEVIC, A. PUDA, A. SCHONEGGER, K. BAGIENSKI et. al.

Basic information

Original name

Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2

Authors

KLAMPFL, T. (40 Austria), J. MILOSEVIC (40 Austria), A. PUDA (40 Austria), A. SCHONEGGER (40 Austria), K. BAGIENSKI (40 Austria), T. BERG (40 Austria), A. HARUTYUNYAN (40 Austria), B. GISSLINGER (40 Austria), E. RUMI (380 Italy), L. MALCOVATI (380 Italy), D. PIETRA (380 Italy), Ch. ELENA (380 Italy), M G DELLA PORTA (380 Italy), L. PIERI (380 Italy), P. GUGLIELMELLI (380 Italy), Ch. BOCK (40 Austria), Michael DOUBEK (203 Czech Republic, belonging to the institution), Dana DVOŘÁKOVÁ (203 Czech Republic, guarantor, belonging to the institution), N. SUVAJDZIC (804 Ukraine), D. TOMIN (804 Ukraine), N. TOSIC (804 Ukraine), Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), M. STEURER (40 Austria), S. PAVLOVIC (804 Ukraine), A. VANNUCCHI (804 Ukraine), M. CAZZOLA (380 Italy), H. GISSLINGER (40 Austria) and R. KRALOVICS (40 Austria)

Edition

PLOS ONE, Public Library of Science, 2013, 1932-6203

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.534

RIV identification code

RIV/00216224:14740/13:00070753

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1371/journal.pone.0077819

UT WoS

000326019400137

Keywords in English

CBL; DDB1; LMO2; myeloid malignancies target

Abstract

V originále

Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

MSM0021622430, plan (intention)

Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies

Files attached

EL_1138599_Complex_patterns.pdf

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Cite

KLAMPFL, T., J. MILOSEVIC, A. PUDA, A. SCHONEGGER, K. BAGIENSKI, T. BERG, A. HARUTYUNYAN, B. GISSLINGER, E. RUMI, L. MALCOVATI, D. PIETRA, Ch. ELENA, M G DELLA PORTA, L. PIERI, P. GUGLIELMELLI, Ch. BOCK, Michael DOUBEK, Dana DVOŘÁKOVÁ, N. SUVAJDZIC, D. TOMIN, N. TOSIC, Zdeněk RÁČIL, M. STEURER, S. PAVLOVIC, A. VANNUCCHI, M. CAZZOLA, H. GISSLINGER and R. KRALOVICS. Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2. PLOS ONE. Public Library of Science, 2013, vol. 8, No 10, p. "nestránkováno", 10 pp. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0077819.

@article{1138599,
   author = {Klampfl, T. and Milosevic, J. and Puda, A. and Schonegger, A. and Bagienski, K. and Berg, T. and Harutyunyan, A. and Gisslinger, B. and Rumi, E. and Malcovati, L. and Pietra, D. and Elena, Ch. and Della Porta, M G and Pieri, L. and Guglielmelli, P. and Bock, Ch. and Doubek, Michael and Dvořáková, Dana and Suvajdzic, N. and Tomin, D. and Tosic, N. and Ráčil, Zdeněk and Steurer, M. and Pavlovic, S. and Vannucchi, A. and Cazzola, M. and Gisslinger, H. and Kralovics, R.},
   article_number = {10},
   doi = {http://dx.doi.org/10.1371/journal.pone.0077819},
   keywords = {CBL; DDB1; LMO2; myeloid malignancies target},
   language = {eng},
   issn = {1932-6203},
   journal = {PLOS ONE},
   title = {Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2},
   url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077819},
   volume = {8},
   year = {2013}
}

TY  - JOUR
ID  - 1138599
AU  - Klampfl, T. - Milosevic, J. - Puda, A. - Schonegger, A. - Bagienski, K. - Berg, T. - Harutyunyan, A. - Gisslinger, B. - Rumi, E. - Malcovati, L. - Pietra, D. - Elena, Ch. - Della Porta, M G - Pieri, L. - Guglielmelli, P. - Bock, Ch. - Doubek, Michael - Dvořáková, Dana - Suvajdzic, N. - Tomin, D. - Tosic, N. - Ráčil, Zdeněk - Steurer, M. - Pavlovic, S. - Vannucchi, A. - Cazzola, M. - Gisslinger, H. - Kralovics, R.
PY  - 2013
TI  - Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2
JF  - PLOS ONE
VL  - 8
IS  - 10
SP  - "nestránkováno"
EP  - "nestránkováno"
PB  - Public Library of Science
SN  - 19326203
KW  - CBL
KW  - DDB1
KW  - LMO2
KW  - myeloid malignancies target
UR  - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077819
L2  - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077819
N2  - Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized.
ER  -

KLAMPFL, T., J. MILOSEVIC, A. PUDA, A. SCHONEGGER, K. BAGIENSKI, T. BERG, A. HARUTYUNYAN, B. GISSLINGER, E. RUMI, L. MALCOVATI, D. PIETRA, Ch. ELENA, M G DELLA PORTA, L. PIERI, P. GUGLIELMELLI, Ch. BOCK, Michael DOUBEK, Dana DVOŘÁKOVÁ, N. SUVAJDZIC, D. TOMIN, N. TOSIC, Zdeněk RÁČIL, M. STEURER, S. PAVLOVIC, A. VANNUCCHI, M. CAZZOLA, H. GISSLINGER and R. KRALOVICS. Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2. \textit{PLOS ONE}. Public Library of Science, 2013, vol.~8, No~10, p.~''nestránkováno'', 10 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0077819.

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