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SDHB-related pheochromocytoma and paraganglioma penetrance and genotype–phenotype correlations

  • Original Article – Cancer Research
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Abstract

Purpose

Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma (PHEO/PGL). Limited information is available concerning PHEO/PGL penetrance among SDHB mutation carriers with regards to primary tumor location, specific mutation type, and gender. We assessed PHEO/PGL penetrance in SDHB mutation carriers and described the clinical presentation and disease course.

Methods

Asymptomatic relatives (N = 611) of 103 index patients were tested for SDHB mutations. Mutation carriers (N = 328) were offered PHEO/PGL screening, of which 241 participated and were included in penetrance analysis. For additional disease outcome analysis, the 103 index patients and 40 screened individuals who developed PHEO/PGL were included. Clinical data were collected between October 2004 and June 2016.

Results

Forty (16.60%) of the 241 screened individuals developed PHEO/PGL during the study. The penetrance estimate in this population was 49.80% (95% CI 29–74.9) at 85 years. A significantly higher age-related penetrance of disease was observed in males compared to females, with 50% penetrance achieved at age 74 vs. not reached. Age-related penetrance analysis demonstrated 4 mutations (Ile127Ser, IVS1+1G>T, Exon 1 deletion, Arg90X) presenting with a slower rate of disease development (50% penetrance ages, respectively: not achieved, 70, 63, 61 years) compared to Arg46X and Val140Phe mutations (50% penetrance at 38 years).

Conclusions

Here, we found a higher estimated penetrance compared to several other studies, and a striking difference in age-related penetrance between male and female SDHB mutation carriers with no association between mutation and gender or tumor location.

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Authors and Affiliations

  1. Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, 1E-3140, Bethesda, MD, 20892-1109, USA

    Ivana Jochmanova, Katherine I. Wolf, Kathryn S. King, Joan Nambuba, Victoria Martucci, Karen T. Adams, Tamara Prodanov & Karel Pacak

  2. 1st Department of Internal Medicine, Medical Faculty of P. J. Šafárik University in Košice, Trieda SNP 1, 04011, Košice, Slovakia

    Ivana Jochmanova & Ivica Lazurova

  3. Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA

    Robert Wesley

  4. Section on Developmental Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    Margarita Raygada

  5. Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Antonio Tito Fojo

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  1. Ivana Jochmanova
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  2. Katherine I. Wolf
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Correspondence to Karel Pacak.

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This work was supported, in part, by the Intramural Research Program of the NIH, NICHD.

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Jochmanova, I., Wolf, K.I., King, K.S. et al. SDHB-related pheochromocytoma and paraganglioma penetrance and genotype–phenotype correlations. J Cancer Res Clin Oncol 143, 1421–1435 (2017). https://doi.org/10.1007/s00432-017-2397-3

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