Bausch, Birke, Schiavi, Francesca, Ni, Ying, Welander, Jenny, Patocs, Attila, Ngeow, Joanne ORCID: 0000-0003-1558-3627, Wellner, Ulrich ORCID: 0000-0002-8632-166X, Malinoc, Angelica, Taschin, Elisa, Barbon, Giovanni, Lanza, Virginia, Soederkvist, Peter, Stenman, Adam ORCID: 0000-0003-3248-7629, Larsson, Catharina, Svahn, Fredrika, Chen, Jin-Lian, Marquard, Jessica, Fraenkel, Merav, Walter, Martin A., Peczkowska, Mariola, Prejbisz, Aleksander ORCID: 0000-0001-7085-0244, Jarzab, Barbara ORCID: 0000-0001-9811-9584, Hasse-Lazar, Kornelia ORCID: 0000-0002-6430-0980, Petersenn, Stephan, Moeller, Lars C., Meyer, Almuth, Reisch, Nicole, Trupka, Arnold, Brase, Christoph, Galiano, Matthias, Preuss, Simon F., Kwok, Pingling, Lendvai, Nikoletta, Berisha, Gani, Makay, Ozer, Boedeker, Carsten C., Weryha, Georges, Racz, Karoly, Januszewicz, Andrzej, Walz, Martin K., Gimm, Oliver, Opocher, Giuseppe ORCID: 0000-0002-9845-9623, Eng, Charis and Neumann, Hartmut P. H. (2017). Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention. JAMA Oncol., 3 (9). S. 1204 - 1213. CHICAGO: AMER MEDICAL ASSOC. ISSN 2374-2445

Full text not available from this repository.

Abstract

IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P < .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bausch, BirkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiavi, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ni, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Welander, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patocs, AttilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ngeow, JoanneUNSPECIFIEDorcid.org/0000-0003-1558-3627UNSPECIFIED
Wellner, UlrichUNSPECIFIEDorcid.org/0000-0002-8632-166XUNSPECIFIED
Malinoc, AngelicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taschin, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barbon, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lanza, VirginiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soederkvist, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stenman, AdamUNSPECIFIEDorcid.org/0000-0003-3248-7629UNSPECIFIED
Larsson, CatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Svahn, FredrikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, Jin-LianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marquard, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fraenkel, MeravUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, Martin A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peczkowska, MariolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prejbisz, AleksanderUNSPECIFIEDorcid.org/0000-0001-7085-0244UNSPECIFIED
Jarzab, BarbaraUNSPECIFIEDorcid.org/0000-0001-9811-9584UNSPECIFIED
Hasse-Lazar, KorneliaUNSPECIFIEDorcid.org/0000-0002-6430-0980UNSPECIFIED
Petersenn, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moeller, Lars C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, AlmuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reisch, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trupka, ArnoldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brase, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galiano, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preuss, Simon F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwok, PinglingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lendvai, NikolettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berisha, GaniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Makay, OzerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boedeker, Carsten C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weryha, GeorgesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Racz, KarolyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Januszewicz, AndrzejUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walz, Martin K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gimm, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Opocher, GiuseppeUNSPECIFIEDorcid.org/0000-0002-9845-9623UNSPECIFIED
Eng, CharisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumann, Hartmut P. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-220800
DOI: 10.1001/jamaoncol.2017.0223
Journal or Publication Title: JAMA Oncol.
Volume: 3
Number: 9
Page Range: S. 1204 - 1213
Date: 2017
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2374-2445
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GERMLINE MUTATIONS; PITUITARY-ADENOMA; LARGE COHORT; HEREDITARY; ASSOCIATION; PENETRANCE; PREVALENCE; VARIANTS; FEATURES; PATIENTMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22080

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item