Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis

Johanna Sandgren; Teresita Diaz de Ståhl; Robin Andersson; Uwe Menzel; Arkadiusz Piotrowski; Helena Nord; Martin Bäckdahl; Nimrod B Kiss; Michael Brauckhoff; Jan Komorowski; Henning Dralle; Ola Hessman; Catharina Larsson; Göran Akerström; Carl Bruder; Jan P Dumanski; Gunnar Westin

doi:10.1677/ERC-09-0310

Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis

Johanna Sandgren, Teresita Diaz de Ståhl, Robin Andersson, Uwe Menzel, Arkadiusz Piotrowski, Helena Nord, Martin Bäckdahl, Nimrod B Kiss, Michael Brauckhoff, Jan Komorowski, Henning Dralle, Ola Hessman, Catharina Larsson, Göran Akerström, Carl Bruder, Jan P Dumanski, Gunnar Westin

26 Citations (Scopus)

Abstract

Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (≥32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (≥14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.

Original language	English
Journal	Endocrine - Related Cancer
Volume	17
Issue number	3
Pages (from-to)	561-79
Number of pages	19
ISSN	1351-0088
DOIs	https://doi.org/10.1677/ERC-09-0310
Publication status	Published - Sept 2010
Externally published	Yes

Keywords

Adolescent
Adrenal Gland Neoplasms
Adult
Aged
Comparative Genomic Hybridization
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Mutation
Paraganglioma
Reverse Transcriptase Polymerase Chain Reaction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1677/ERC-09-0310

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Sandgren, J., Diaz de Ståhl, T., Andersson, R., Menzel, U., Piotrowski, A., Nord, H., Bäckdahl, M., Kiss, N. B., Brauckhoff, M., Komorowski, J., Dralle, H., Hessman, O., Larsson, C., Akerström, G., Bruder, C., Dumanski, J. P., & Westin, G. (2010). Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis. Endocrine - Related Cancer, 17(3), 561-79. https://doi.org/10.1677/ERC-09-0310

Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis. / Sandgren, Johanna; Diaz de Ståhl, Teresita; Andersson, Robin et al.
In: Endocrine - Related Cancer, Vol. 17, No. 3, 09.2010, p. 561-79.

Research output: Contribution to journal › Journal article › Research › peer-review

Sandgren, J, Diaz de Ståhl, T, Andersson, R, Menzel, U, Piotrowski, A, Nord, H, Bäckdahl, M, Kiss, NB, Brauckhoff, M, Komorowski, J, Dralle, H, Hessman, O, Larsson, C, Akerström, G, Bruder, C, Dumanski, JP & Westin, G 2010, 'Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis', Endocrine - Related Cancer, vol. 17, no. 3, pp. 561-79. https://doi.org/10.1677/ERC-09-0310

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title = "Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis",

abstract = "Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (≥32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (≥14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.",

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T1 - Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis

AU - Sandgren, Johanna

AU - Diaz de Ståhl, Teresita

AU - Andersson, Robin

AU - Menzel, Uwe

AU - Piotrowski, Arkadiusz

AU - Nord, Helena

AU - Bäckdahl, Martin

AU - Kiss, Nimrod B

AU - Brauckhoff, Michael

AU - Komorowski, Jan

AU - Dralle, Henning

AU - Hessman, Ola

AU - Larsson, Catharina

AU - Akerström, Göran

AU - Bruder, Carl

AU - Dumanski, Jan P

AU - Westin, Gunnar

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N2 - Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (≥32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (≥14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.

AB - Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (≥32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (≥14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.

KW - Adolescent

KW - Adrenal Gland Neoplasms

KW - Adult

KW - Aged

KW - Comparative Genomic Hybridization

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Paraganglioma

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1677/ERC-09-0310

DO - 10.1677/ERC-09-0310

M3 - Journal article

C2 - 20410162

SN - 1351-0088

VL - 17

SP - 561

EP - 579

JO - Endocrine - Related Cancer

JF - Endocrine - Related Cancer

IS - 3

ER -

Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis

Abstract

Keywords

UN SDGs

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