Genomic and functional overlap between somatic and germline chromosomal rearrangements

Sebastiaan van Heesch; Marieke Simonis; Markus J van Roosmalen; Vamsee Pillalamarri; Harrison Brand; Ewart W Kuijk; Kim L de Luca; Nico Lansu; A Koen Braat; Androniki Menelaou; Wensi Hao; Jeroen Korving; Simone Snijder; Lars T van der Veken; Ron Hochstenbach; Alida C Knegt; Karen Duran; Ivo Renkens; Najla Alekozai; Myrthe Jager; Sarah Vergult; Björn Menten; Ewart de Bruijn; Sander Boymans; Elly Ippel; Ellen van Binsbergen; Michael E Talkowski; Klaske Lichtenbelt; Edwin Cuppen; Wigard P Kloosterman

doi:10.1016/j.celrep.2014.11.022

Genomic and functional overlap between somatic and germline chromosomal rearrangements

Sebastiaan van Heesch, Marieke Simonis, Markus J van Roosmalen, Vamsee Pillalamarri, Harrison Brand, Ewart W Kuijk, Kim L de Luca, Nico Lansu, A Koen Braat, Androniki Menelaou, Wensi Hao, Jeroen Korving, Simone Snijder, Lars T van der Veken, Ron Hochstenbach, Alida C Knegt, Karen Duran, Ivo Renkens, Najla Alekozai, Myrthe JagerSarah Vergult, Björn Menten, Ewart de Bruijn, Sander Boymans, Elly Ippel, Ellen van Binsbergen, Michael E Talkowski, Klaske Lichtenbelt, Edwin Cuppen, Wigard P Kloosterman

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

Originele taal-2	Engels
Pagina's (van-tot)	2001-10
Aantal pagina's	10
Tijdschrift	Cell reports
Volume	9
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1016/j.celrep.2014.11.022
Status	Gepubliceerd - 24 dec. 2014
Extern gepubliceerd	Ja

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10.1016/j.celrep.2014.11.022

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van Heesch, S., Simonis, M., van Roosmalen, M. J., Pillalamarri, V., Brand, H., Kuijk, E. W., de Luca, K. L., Lansu, N., Braat, A. K., Menelaou, A., Hao, W., Korving, J., Snijder, S., van der Veken, L. T., Hochstenbach, R., Knegt, A. C., Duran, K., Renkens, I., Alekozai, N., ... Kloosterman, W. P. (2014). Genomic and functional overlap between somatic and germline chromosomal rearrangements. Cell reports, 9(6), 2001-10. https://doi.org/10.1016/j.celrep.2014.11.022

@article{255cb1b154f845efb82ed69efc1726e5,

title = "Genomic and functional overlap between somatic and germline chromosomal rearrangements",

abstract = "Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted. ",

keywords = "Animals, Chromosome Aberrations, Chromosome Breakpoints, Chromosomes, Human/genetics, Congenital Abnormalities/genetics, DNA-Binding Proteins/genetics, Forkhead Transcription Factors/genetics, Gene Rearrangement, Genome, Human, Germ-Line Mutation, HEK293 Cells, Humans, MicroRNAs/genetics, Repressor Proteins/genetics, Transcription Factors/genetics, Zebrafish",

author = "{van Heesch}, Sebastiaan and Marieke Simonis and {van Roosmalen}, {Markus J} and Vamsee Pillalamarri and Harrison Brand and Kuijk, {Ewart W} and {de Luca}, {Kim L} and Nico Lansu and Braat, {A Koen} and Androniki Menelaou and Wensi Hao and Jeroen Korving and Simone Snijder and {van der Veken}, {Lars T} and Ron Hochstenbach and Knegt, {Alida C} and Karen Duran and Ivo Renkens and Najla Alekozai and Myrthe Jager and Sarah Vergult and Bj{\"o}rn Menten and {de Bruijn}, Ewart and Sander Boymans and Elly Ippel and {van Binsbergen}, Ellen and Talkowski, {Michael E} and Klaske Lichtenbelt and Edwin Cuppen and Kloosterman, {Wigard P}",

year = "2014",

month = dec,

day = "24",

doi = "10.1016/j.celrep.2014.11.022",

language = "English",

volume = "9",

pages = "2001--10",

journal = "Cell reports",

issn = "2211-1247",

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van Heesch, S, Simonis, M, van Roosmalen, MJ, Pillalamarri, V, Brand, H, Kuijk, EW, de Luca, KL, Lansu, N, Braat, AK, Menelaou, A, Hao, W, Korving, J, Snijder, S, van der Veken, LT, Hochstenbach, R, Knegt, AC, Duran, K, Renkens, I, Alekozai, N, Jager, M, Vergult, S, Menten, B, de Bruijn, E, Boymans, S, Ippel, E, van Binsbergen, E, Talkowski, ME, Lichtenbelt, K, Cuppen, E & Kloosterman, WP 2014, 'Genomic and functional overlap between somatic and germline chromosomal rearrangements', Cell reports, vol. 9, nr. 6, blz. 2001-10. https://doi.org/10.1016/j.celrep.2014.11.022

TY - JOUR

T1 - Genomic and functional overlap between somatic and germline chromosomal rearrangements

AU - van Heesch, Sebastiaan

AU - Simonis, Marieke

AU - van Roosmalen, Markus J

AU - Pillalamarri, Vamsee

AU - Brand, Harrison

AU - Kuijk, Ewart W

AU - de Luca, Kim L

AU - Lansu, Nico

AU - Braat, A Koen

AU - Menelaou, Androniki

AU - Hao, Wensi

AU - Korving, Jeroen

AU - Snijder, Simone

AU - van der Veken, Lars T

AU - Hochstenbach, Ron

AU - Knegt, Alida C

AU - Duran, Karen

AU - Renkens, Ivo

AU - Alekozai, Najla

AU - Jager, Myrthe

AU - Vergult, Sarah

AU - Menten, Björn

AU - de Bruijn, Ewart

AU - Boymans, Sander

AU - Ippel, Elly

AU - van Binsbergen, Ellen

AU - Talkowski, Michael E

AU - Lichtenbelt, Klaske

AU - Cuppen, Edwin

AU - Kloosterman, Wigard P

PY - 2014/12/24

Y1 - 2014/12/24

N2 - Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

AB - Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

KW - Animals

KW - Chromosome Aberrations

KW - Chromosome Breakpoints

KW - Chromosomes, Human/genetics

KW - Congenital Abnormalities/genetics

KW - DNA-Binding Proteins/genetics

KW - Forkhead Transcription Factors/genetics

KW - Gene Rearrangement

KW - Genome, Human

KW - Germ-Line Mutation

KW - HEK293 Cells

KW - Humans

KW - MicroRNAs/genetics

KW - Repressor Proteins/genetics

KW - Transcription Factors/genetics

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=84919839764&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2014.11.022

DO - 10.1016/j.celrep.2014.11.022

M3 - Article

C2 - 25497101

SN - 2211-1247

VL - 9

SP - 2001

EP - 2010

JO - Cell reports

JF - Cell reports

IS - 6

ER -

Genomic and functional overlap between somatic and germline chromosomal rearrangements

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