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Welander, Jenny
Publications (10 of 19) Show all publications
Welander, J., Lysiak, M., Brauckhoff, M., Brunaud, L., Söderkvist, P. & Gimm, O. (2018). Activating FGFR1 mutations in sporadic pheochromocytoma. World Journal of Surgery, 42(2), 482-489
Open this publication in new window or tab >>Activating FGFR1 mutations in sporadic pheochromocytoma
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2018 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 482-489Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas are neuroendocrine tumors of the adrenal glands that cause hypertension. More than a third of the cases are associated with hereditary mutations in a growing list of susceptibility genes, some of which are also somatically altered in sporadic pheochromocytomas. However, for the majority of sporadic pheochromocytomas, a genetic explanation is still lacking. Here we investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples, and discovered on average 33 non-silent somatic mutations per tumor. One of the recurrently mutated genes was FGFR1, encoding the fibroblast growth factor receptor 1, which was recently revealed as an oncogene in pilocytic astrocytoma and childhood glioblastoma. Including a subsequent analysis of a larger cohort, activating FGFR1  mutations were detected in three of 80 sporadic pheochromocytomas (3.8%). Gene expression microarray profiling showed that these tumors clustered with NF1- RET- and HRAS-mutated pheochromocytomas, indicating activation of the MAPK and PI3K-AKT signal transduction pathways. The results advance our biological understanding of pheochromocytoma and suggest that somatic FGFR1 activation is an important event in a subset of these tumors.

Place, publisher, year, edition, pages
Springer, 2018
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114805 (URN)10.1007/s00268-017-4320-0 (DOI)000419886700025 ()29159601 (PubMedID)
Note

Funding agencies: Linkoping University; Swedish Cancer Society; FORSS; LiU Cancer

Available from: 2015-03-04 Created: 2015-03-04 Last updated: 2019-05-03Bibliographically approved
Paulsson, J. O., Svahn, F., Welander, J., Brunaud, L., Söderkvist, P., Gimm, O., . . . Juhlin, C. C. (2016). Editorial Material: Absence of the BRAF V600E mutation in pheochromocytoma in JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol 39, issue 6, pp 715-716. Journal of Endocrinological Investigation, 39(6), 715-716
Open this publication in new window or tab >>Editorial Material: Absence of the BRAF V600E mutation in pheochromocytoma in JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, vol 39, issue 6, pp 715-716
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2016 (English)In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 39, no 6, p. 715-716Article in journal, Editorial material (Other academic) Published
Abstract [en]

Purpose Pheochromocytomas (PCCs) are rare endocrine tumors originating from the adrenal medulla. These tumors display a highly heterogeneous mutation profile, and a substantial part of the causative genetic events remains to be explained. Recent studies have reported presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. This study sought to further investigate the occurrence of the BRAF V600E mutation in these tumors. Methods A cohort of 110 PCCs was screened for the BRAF V600E mutation using direct Sanger sequencing. Results All cases investigated displayed wild-type sequences at nucleotide 1799 in the BRAF gene. Conclusions Taken together with all previously screened tumors up to date, only 1 BRAF V600E mutation has been found among 361 PCCs. These findings imply that the BRAF V600E mutation is a rare event in pheochromocytoma.

Place, publisher, year, edition, pages
SPRINGER, 2016
Keywords
Adrenal; Pheochromocytoma; Sequencing; BRAF; Mutation
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-129146 (URN)10.1007/s40618-015-0420-6 (DOI)000375920000013 ()26710756 (PubMedID)
Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2018-04-25
Stenman, A., Welander, J., Gustavsson, I., Brunaud, L., Backdahl, M., Söderkvist, P., . . . Larsson, C. (2016). HRAS mutation prevalence and associated expression patterns in pheochromocytoma. Genes, Chromosomes and Cancer, 55(5), 452-459
Open this publication in new window or tab >>HRAS mutation prevalence and associated expression patterns in pheochromocytoma
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2016 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 55, no 5, p. 452-459Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background and recent gene expression profiling studies have shown that PCC and PGL (together PPGL) alter either kinase signaling pathways or the pseudo-hypoxia response pathway dependent of the genetic composition. Recurrent mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been verified in sporadic PPGLs. In order to further establish the HRAS mutation frequency and to characterize the associated expression profiles of HRAS mutated tumors, 156 PPGLs for exon 2 and 3 hotspot mutations in the HRAS gene was screened, and compared with microarray-based gene expression profiles for 93 of the cases. The activating HRAS mutations G13R, Q61R, and Q61K were found in 10/142 PCC (7.0%) and a Q61L mutation was revealed in 1/14 PGL (7.1%). All HRAS mutated cases included in the mRNA expression profiling grouped in Cluster 2, and 21 transcripts were identified as altered when comparing the mutated tumors with 91 HRAS wild-type PPGL. Somatic HRAS mutations were not revealed in cases with known PPGL susceptibility gene mutations and all HRAS mutated cases were benign. The HRAS mutation prevalence of all PPGL published up to date is 5.2% (49/950), and 8.8% (48/548) among cases without a known PPGL susceptibility gene mutation. The findings support a role of HRAS mutations as a somatic driver event in benign PPGL without other known susceptibility gene mutations. HRAS mutated PPGL cluster together with NF1- and RET-mutated tumors associated with activation of kinase-signaling pathways.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127407 (URN)10.1002/gcc.22347 (DOI)000372913800005 ()26773571 (PubMedID)
Note

Funding Agencies|Swedish Cancer Foundation; StratCan; Swedish Research Council; Cancer Research Foundations of Radiumhemmet; Karolinska Institutet; Stockholm County Council

Available from: 2016-05-02 Created: 2016-04-26 Last updated: 2018-04-25
Welander, J. (2015). Genetic Alterations in Pheochromocytoma and Paraganglioma. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Genetic Alterations in Pheochromocytoma and Paraganglioma
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pheochromocytomas and paragangliomas are neuroendocrine tumors that arise from neural crest-derived cells of the adrenal medulla and the extra-adrenal paraganglia. They cause hypertension due to an abnormally high production of catecholamines (mainly adrenaline and noradrenaline), with symptoms including recurrent episodes of headache, palpitations and sweating, and an increased risk of cardiovascular disease. Malignancy in the form of distant metastases occurs in 10-15% of the patients. The malignant cases are difficult to predict and cure, and have a poor prognosis. About a third of pheochromocytomas and paragangliomas are caused by hereditary mutations in a growing list of known susceptibility genes. However, the cause of the remaining, sporadic, tumors is still largely unknown. The aim of this thesis project has been to further characterize the genetic background of pheochromocytomas and paragangliomas, with a focus on the sporadic tumors.

First, we investigated the role of the genes known from the familial tumors in the sporadic form of the disease. By studying mutations, copy number variations, DNA methylation and gene expression, we found that many of the known susceptibility genes harbor somatic alterations in sporadic pheochromocytomas. Particularly, we found that the NF1 gene, which plays an important role in suppressing cell growth and proliferation by regulating the RASMAPK pathway, was inactivated by mutations in more than 20% of the cases. The mutations occurred together with deletions of the normal allele and were associated with a reduced NF1 gene expression and a specific hormone profile. We also detected activating mutations in the gene EPAS1, which encodes HIF-2α, in a subset of sporadic cases. Microarray analysis of gene expression showed that several genes involved in angiogenesis and cell metabolism were upregulated in EPAS1-mutated tumors, which is in agreement with the role of HIF-2α in the cellular response to hypoxia. In order to comprehensively investigate all the known susceptibility genes in a larger patient cohort, we designed a targeted next-generation sequencing approach and could conclude that it was fast and cost-efficient for genetic testing of pheochromocytomas and paragangliomas. The results showed that about 40% of the sporadic cases had mutations in the tested genes. The majority of the mutations were somatic, but some apparently sporadic cases in fact carried germline mutations. Such knowledge of the genetic background can be of importance to facilitate early detection and correct treatment of pheochromocytomas, paragangliomas and potential co-occurring cancers, and also to identify relatives that might be at risk. By sequencing all the coding regions of the genome, the exome, we then identified recurrent activating mutations in a novel gene, in which mutations have previously only been reported in subgroups of brain tumors. The identified mutations are proposed to cause constitutive activation of the encoded receptor tyrosine kinase, resulting in the activation of downstream kinase signaling pathways that promote cell growth and proliferation.

In summary, the studies increase our biological understanding of pheochromocytoma and paraganglioma, and possibly also co-occurring cancers in which the same genes and pathways are involved. Together with the findings of other scientific studies, our results may contribute to the development of future treatment options.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. p. 64
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1439
Keywords
Pheochromocytoma; paraganglioma; genetics; sequencing; cancer; mutation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114806 (URN)10.3384/diss.diva-114806 (DOI)978-91-7519-145-4 (ISBN)
Public defence
2015-04-09, Berzeliussalen, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2015-03-04 Created: 2015-03-04 Last updated: 2019-11-15Bibliographically approved
Stenman, A., Svahn, F., Welander, J., Gustavson, B., Söderkvist, P., Gimm, O. & Juhlin, C. C. (2015). Immunohistochemical NF1 Analysis Does not Predict NF1 Gene Mutation Status in Pheochromocytoma.. Endocrine pathology, 26(1), 9-14
Open this publication in new window or tab >>Immunohistochemical NF1 Analysis Does not Predict NF1 Gene Mutation Status in Pheochromocytoma.
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2015 (English)In: Endocrine pathology, ISSN 1046-3976, E-ISSN 1559-0097, Vol. 26, no 1, p. 9-14Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas (PCCs) are tumors originating from the adrenal medulla displaying a diverse genetic background. While most PCCs are sporadic, about 40 % of the tumors have been associated with constitutional mutations in one of at least 14 known susceptibility genes. As 25 % of sporadic PCCs harbor somatic neurofibromin 1 gene (NF1) mutations, NF1 has been established as the most recurrently mutated gene in PCCs. To be able to pinpoint NF1-related pheochromocytoma (PCC) disease in clinical practice could facilitate the detection of familial cases, but the large size of the NF1 gene makes standard DNA sequencing methods cumbersome. The aim of this study was to examine whether mutations in the NF1 gene could be predicted by immunohistochemistry as a method to identify cases for further genetic characterization. Sixty-seven PCCs obtained from 67 unselected patients for which the somatic and constitutional mutational status of NF1 was known (49 NF1 wild type, 18 NF1 mutated) were investigated for NF1 protein immunoreactivity, and the results were correlated to clinical and genetic data. NF1 immunoreactivity was absent in the majority of the PCCs (44/67; 66 %), including 13 out of 18 cases (72 %) with a somatic or constitutional NF1 mutation. However, only a minority of the NF1 wild-type PCCs (18/49; 37 %) displayed retained NF1 immunoreactivity, thereby diminishing the specificity of the method. We conclude that NF1 immunohistochemistry alone is not a sufficient method to distinguish between NF1-mutated and non-mutated PCCs. In the clinical context, genetic screening therefore remains the most reliable tool to detect NF1-mutated PCCs.

Place, publisher, year, edition, pages
Springer, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-115262 (URN)10.1007/s12022-014-9348-1 (DOI)000350057500002 ()25403449 (PubMedID)
Available from: 2015-03-11 Created: 2015-03-11 Last updated: 2018-04-25Bibliographically approved
Christofer Juhlin, C., Stenman, A., Haglund, F., Clark, V. E., Brown, T. C., Baranoski, J., . . . Carling, T. (2015). Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene. Genes, Chromosomes and Cancer, 54(9), 542-554
Open this publication in new window or tab >>Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene
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2015 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 54, no 9, p. 542-554Article in journal (Refereed) Published
Abstract [en]

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120721 (URN)10.1002/gcc.22267 (DOI)000358384000002 ()26032282 (PubMedID)
Note

Funding Agencies|Stockholm County Council; StratCan, Karolinska Institutet, Stockholm; Agency for Science, Technology and Research, Singapore; Cancer Society in Stockholm, Sweden; Damon Runyon Cancer Research Foundation; Ohse Research Award

Available from: 2015-08-24 Created: 2015-08-24 Last updated: 2018-04-25
Dutta, R. K., Welander, J., Brauckhoff, M., Walz, M., Alesina, P., Arnesen, T., . . . Gimm, O. (2014). Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas [Letter to the editor]. Endocrine-Related Cancer, 21(1), L1-L4
Open this publication in new window or tab >>Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas
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2014 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 1, p. L1-L4Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Bioscientifica, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-106692 (URN)10.1530/ERC-13-0466 (DOI)000334279600001 ()24179102 (PubMedID)
Available from: 2014-05-20 Created: 2014-05-19 Last updated: 2019-12-10Bibliographically approved
Welander, J., Andreasson, A., Brauckhoff, M., Backdahl, M., Larsson, C., Gimm, O. & Söderkvist, P. (2014). Frequent EPAS1/HIF2 alpha exons 9 and 12 mutations in non-familial pheochromocytoma. Endocrine-Related Cancer, 21(3), 495-504
Open this publication in new window or tab >>Frequent EPAS1/HIF2 alpha exons 9 and 12 mutations in non-familial pheochromocytoma
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2014 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 3, p. 495-504Article in journal (Refereed) Published
Abstract [en]

Pheochromocytomas are neuroendocrine tumors arising from the adrenal medulla. While heritable mutations are frequently described, less is known about the genetics of sporadic pheochromocytoma. Mutations in genes involved in the cellular hypoxia response have been identified in tumors, and recently EPAS1, encoding HIF2 alpha, has been revealed to be a new gene involved in the pathogenesis of pheochromocytoma and abdominal paraganglioma. The aim of this study was to further characterize EPAS1 alterations in non-familial pheochromocytomas. Tumor DNA from 42 adrenal pheochromocytoma cases with apparently sporadic presentation, without known hereditary mutations in predisposing genes, were analyzed for mutations in EPAS1 by sequencing of exons 9 and 12, which contain the two hydroxylation sites involved in HIF2a degradation, and also exon 2. In addition, the copy number at the EPAS1 locus as well as transcriptome-wide gene expression were studied by DNA and RNA microarray analyses, respectively. We identified six missense EPAS1 mutations, three in exon 9 and three in exon 12, in five of 42 pheochromocytomas (12%). The mutations were both somatic and constitutional, and had no overlap in 11 cases (26%) with somatic mutations in NF1 or RET. One sample had two different EPAS1 mutations, shown by cloning to occur in cis, possibly indicating a novel mechanism of HIF2a stabilization through inactivation of both hydroxylation sites. One of the tumors with an EPAS1 mutation also had a gain in DNA copy number at the EPAS1 locus. All EPAS1-mutated tumors displayed a pseudo-hypoxic gene expression pattern, indicating an oncogenic role of the identified mutations.

Place, publisher, year, edition, pages
BioScientifica, 2014
Keywords
EPAS1; HIF2A; pheochromocytoma; mutation; copy number; gene expression
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112842 (URN)10.1530/ERC-13-0384 (DOI)000344787700030 ()24741025 (PubMedID)
Note

Funding Agencies|University of Linkoping; Swedish Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; StratCan at Karolinska Institutet

Available from: 2015-01-08 Created: 2014-12-17 Last updated: 2018-04-25
Welander, J., Andreasson, A., Juhlin, C. C., Wiseman, R. W., Backdahl, M., Hoog, A., . . . Söderkvist, P. (2014). Rare Germline Mutations Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma. Journal of Clinical Endocrinology and Metabolism, 99(7), E1352-E1360
Open this publication in new window or tab >>Rare Germline Mutations Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma
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2014 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 7, p. E1352-E1360Article in journal (Refereed) Published
Abstract [en]

Context: Pheochromocytomas and paragangliomas have a highly diverse genetic background, with a third of the cases carrying a germline mutation in 1 of 14 identified genes. Objective: This study aimed to evaluate next-generation sequencing for more efficient genetic testing of pheochromocytoma and paraganglioma and to establish germline and somatic mutation frequencies for all known susceptibility genes. Design: A targeted next-generation sequencing approach on an Illumina MiSeq instrument was used for a mutation analysis in 86 unselected pheochromocytoma and paraganglioma tumor samples. The study included the genes EGLN1, EPAS1, KIF1B beta, MAX, MEN1, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL. Results were verified in tumor and constitutional DNA with Sanger sequencing. Results: In all cases with clinical syndromes or known germline mutations, a mutation was detected in the expected gene. Among 68 nonfamilial tumors, 32 mutations were identified in 28 of the samples (41%), including germline mutations in EGLN1, KIF1B beta, SDHA, SDHB, and TMEM127 and somatic mutations in EPAS1, KIF1B beta, MAX, NF1, RET, and VHL, including one double monoallelic EPAS1 mutation. Conclusions: Targeted next-generation sequencing proved to be fast and cost effective for the genetic analysis of pheochromocytoma and paraganglioma. More than half of the tumors harbored mutations in the investigated genes. Notably, 7% of the apparently sporadic cases carried germline mutations, highlighting the importance of comprehensive genetic testing. KIF1B beta, which previously has not been investigated in a large cohort, appears to be an equally important tumor suppressor as MAX and TMEM127 and could be considered for genetic testing of these patients.

Place, publisher, year, edition, pages
Endocrine Society, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-111616 (URN)10.1210/jc.2013-4375 (DOI)000342341000026 ()24694336 (PubMedID)
Note

Funding Agencies|University of Linkoping; LiU Cancer Network; Swedish Research Council; Cancer Society in Stockholm; Swedish Cancer Society; StratCan at Karolinska Institutet; Genetics Services Unit at the Wisconsin National Primate Research Center [P51RR000167/P51OD011106]

Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2018-04-25
Kugelberg, J., Welander, J., Schiavi, F., Fassina, A., Backdahl, M., Larsson, C., . . . Gimm, O. (2014). Role of SDHAF2 and SDHD in von Hippel-Lindau Associated Pheochromocytomas. World Journal of Surgery, 38(3), 724-732
Open this publication in new window or tab >>Role of SDHAF2 and SDHD in von Hippel-Lindau Associated Pheochromocytomas
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2014 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 38, no 3, p. 724-732Article in journal (Refereed) Published
Abstract [en]

Background Pheochromocytomas (PCCs) develop from the adrenal medulla and are often part of a hereditary syndrome such as von Hippel-Lindau (VHL) syndrome. In VHL, only about 30 % of patients with a VHL missense mutation develop PCCs. Thus, additional genetic events leading to formation of such tumors in patients with VHL syndrome are sought. SDHAF2 (previously termed SDH5) and SDHD are both located on chromosome 11q and are required for the function of mitochondrial complex II. While SDHAF2 has been shown to be mutated in patients with paragangliomas (PGLs), SDHD mutations have been found both in patients with PCCs and in patients with PGLs. Materials and methods Because loss of 11q is a common event in VHL-associated PCCs, we aimed to investigate whether SDHAF2 and SDHD are targets. In the present study, 41 VHL-associated PCCs were screened for mutations and loss of heterozygosity (LOH) in SDHAF2 or SDHD. Promoter methylation, as well as mRNA expression of SDHAF2 and SDHD, was studied. In addition, immunohistochemistry (IHC) of SDHB, known to be a universal marker for loss of any part the SDH complex, was conducted. Results and conclusions LOH was found in more than 50 % of the VHL-associated PCCs, and was correlated with a significant decrease (p less than 0.05) in both SDHAF2 and SDHD mRNA expression, which may be suggestive of a pathogenic role. However, while SDHB protein expression as determined by IHC in a small cohort of tumors was lower in PCCs than in the surrounding adrenal cortex, there was no obvious correlation with LOH or the level of SDHAF2/SDHD mRNA expression. In addition, the lack of mutations and promoter methylation in the investigated samples indicates that other events on chromosome 11 might be involved in the development of PCCs in association with VHL syndrome.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-106102 (URN)10.1007/s00268-013-2373-2 (DOI)000333151700030 ()
Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2018-04-25
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