Loss of chromosome Y leads to down regulation of KDM5D and
KDM6C epigenetic modifiers in clear cell renal cell carcinoma

J 2017

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma

ARSENEAULT, M., J. MONLONG, N.S. VASUDEV, R.S. LASKAR, M. SAFISAMGHABADI et. al.

Basic information

Original name

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma

Authors

ARSENEAULT, M. (124 Canada), J. MONLONG (124 Canada), N.S. VASUDEV (124 Canada), R.S. LASKAR (124 Canada), M. SAFISAMGHABADI (124 Canada), P. HARNDEN (826 United Kingdom of Great Britain and Northern Ireland), L. EGEVAD (203 Czech Republic), N. NOURBEHESHT (124 Canada), P. PANICHNANTAKUL (826 United Kingdom of Great Britain and Northern Ireland), I. HOLCATOVA (826 United Kingdom of Great Britain and Northern Ireland), A. BRISUDA (124 Canada), V. JANOUT (124 Canada), H. KOLLAROVA (124 Canada), Lenka FORETOVÁ (203 Czech Republic, guarantor, belonging to the institution), M. NAVRATILOVA (203 Czech Republic), D. MATES (124 Canada), V. JINGA (124 Canada), D. ZARIDZE (56 Belgium), A. MUKERIA (56 Belgium), P. JANDAGHI (250 France), P. BRENNAN (203 Czech Republic), A. BRAZMA (643 Russian Federation), J. TOST (642 Romania), G. SCELO (124 Canada), R.E. BANKS (124 Canada), M. LATHROP (124 Canada), G. BOURQUE (124 Canada) and Y. RIAZALHOSSEINI (124 Canada)

Edition

Scientific Reports, LONDON, NATURE PUBLISHING GROUP, 2017, 2045-2322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.122

RIV identification code

RIV/00216224:14110/17:00098730

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/srep44876

UT WoS

000397186600001

Keywords in English

KDM5D; KDM6C

Abstract

V originále

Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively.

Citovat

ARSENEAULT, M., J. MONLONG, N.S. VASUDEV, R.S. LASKAR, M. SAFISAMGHABADI, P. HARNDEN, L. EGEVAD, N. NOURBEHESHT, P. PANICHNANTAKUL, I. HOLCATOVA, A. BRISUDA, V. JANOUT, H. KOLLAROVA, Lenka FORETOVÁ, M. NAVRATILOVA, D. MATES, V. JINGA, D. ZARIDZE, A. MUKERIA, P. JANDAGHI, P. BRENNAN, A. BRAZMA, J. TOST, G. SCELO, R.E. BANKS, M. LATHROP, G. BOURQUE and Y. RIAZALHOSSEINI. Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma. Scientific Reports. LONDON: NATURE PUBLISHING GROUP, 2017, vol. 7, No 44876, p. 1-8. ISSN 2045-2322. Available from: https://dx.doi.org/10.1038/srep44876.

@article{1398985,
   author = {Arseneault, M. and Monlong, J. and Vasudev, N.S. and Laskar, R.S. and Safisamghabadi, M. and Harnden, P. and Egevad, L. and Nourbehesht, N. and Panichnantakul, P. and Holcatova, I. and Brisuda, A. and Janout, V. and Kollarova, H. and Foretová, Lenka and Navratilova, M. and Mates, D. and Jinga, V. and Zaridze, D. and Mukeria, A. and Jandaghi, P. and Brennan, P. and Brazma, A. and Tost, J. and Scelo, G. and Banks, R.E. and Lathrop, M. and Bourque, G. and Riazalhosseini, Y.},
   article_location = {LONDON},
   article_number = {44876},
   doi = {http://dx.doi.org/10.1038/srep44876},
   keywords = {KDM5D; KDM6C},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific Reports},
   title = {Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma},
   volume = {7},
   year = {2017}
}

TY  - JOUR
ID  - 1398985
AU  - Arseneault, M. - Monlong, J. - Vasudev, N.S. - Laskar, R.S. - Safisamghabadi, M. - Harnden, P. - Egevad, L. - Nourbehesht, N. - Panichnantakul, P. - Holcatova, I. - Brisuda, A. - Janout, V. - Kollarova, H. - Foretová, Lenka - Navratilova, M. - Mates, D. - Jinga, V. - Zaridze, D. - Mukeria, A. - Jandaghi, P. - Brennan, P. - Brazma, A. - Tost, J. - Scelo, G. - Banks, R.E. - Lathrop, M. - Bourque, G. - Riazalhosseini, Y.
PY  - 2017
TI  - Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma
JF  - Scientific Reports
VL  - 7
IS  - 44876
SP  - 1-8
EP  - 1-8
PB  - NATURE PUBLISHING GROUP
SN  - 20452322
KW  - KDM5D
KW  - KDM6C
N2  - Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively.
ER  -

ARSENEAULT, M., J. MONLONG, N.S. VASUDEV, R.S. LASKAR, M. SAFISAMGHABADI, P. HARNDEN, L. EGEVAD, N. NOURBEHESHT, P. PANICHNANTAKUL, I. HOLCATOVA, A. BRISUDA, V. JANOUT, H. KOLLAROVA, Lenka FORETOVÁ, M. NAVRATILOVA, D. MATES, V. JINGA, D. ZARIDZE, A. MUKERIA, P. JANDAGHI, P. BRENNAN, A. BRAZMA, J. TOST, G. SCELO, R.E. BANKS, M. LATHROP, G. BOURQUE and Y. RIAZALHOSSEINI. Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma. \textit{Scientific Reports}. LONDON: NATURE PUBLISHING GROUP, 2017, vol.~7, No~44876, p.~1-8. ISSN~2045-2322. Available from: https://dx.doi.org/10.1038/srep44876.

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