Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 18;13(10):2430.
doi: 10.3390/cancers13102430.

Familial Occurrence of Adult Granulosa Cell Tumors: Analysis of Whole-Genome Germline Variants

Joline F Roze  1 , Joachim Kutzera  2 , Wouter Koole  2 , Margreet G E M Ausems  2 , Kristi Engelstad  3 , Jurgen M J Piek  4 , Cor D de Kroon  5 , René H M Verheijen  1 , Gijs van Haaften  2 , Ronald P Zweemer  1 , Glen R Monroe  1
Affiliations

Familial Occurrence of Adult Granulosa Cell Tumors: Analysis of Whole-Genome Germline Variants

Joline F Roze et al. Cancers (Basel). .

Abstract

Adult granulosa cell tumor (AGCT) is a rare ovarian cancer subtype, with a peak incidence around 50-55 years. Although AGCT can occur in specific syndromes, a genetic predisposition for AGCT has not been identified. The aim of this study is to identify a genetic variant in families with AGCT patients, potentially contributing to tumor evolution. We identified four families, each including two women diagnosed with AGCT. Whole-genome sequencing was performed to identify overlapping germline variants or affected genes. Familial relationship was evaluated using genealogy and genomic analyses. Patient characteristics, medical (family) history, and pedigrees were collected. Findings were compared to a reference group of 33 unrelated AGCT patients. Mean age at diagnosis was 38 years (range from 17 to 60) versus 51 years in the reference group, and seven of eight patients were premenopausal. In two families, three first degree relatives were diagnosed with breast cancer. Furthermore, polycystic ovary syndrome (PCOS) and subfertility was reported in three families. Predicted deleterious variants in PIK3C2G, BMP5, and LRP2 were identified. In conclusion, AGCTs occur in families and could potentially be hereditary. In these families, the age of AGCT diagnosis is lower and cases of breast cancer, PCOS, and subfertility are present. We could not identify an overlapping genetic variant or affected locus that may explain a genetic predisposition for AGCT.

Keywords: FOXL2; granulosa cell tumor; ovarian cancer; sex cord-stromal tumors; whole-genome sequencing.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Family pedigrees. Colors represent diagnosis of AGCT, other cancer or cardiovascular disease. Deceased persons are indicated with a slash (/). Family A. Patients were related via their grandfathers. Family B. The AGCT patients represented mother and daughter. Family C. The AGCT patients represented niece and aunt. Their mother, respectively sister was diagnosed with breast cancer. Patient C2 was involuntarily childless because of subfertility and more cases of subfertility were reported in this family. Family D. The AGCT patients were related through their grandfathers, who were brothers. Both mothers of the patients were diagnosed with breast cancer. One of the patient’s sisters was also involuntarily childless due to subfertility.
Figure 1
Figure 1
Family pedigrees. Colors represent diagnosis of AGCT, other cancer or cardiovascular disease. Deceased persons are indicated with a slash (/). Family A. Patients were related via their grandfathers. Family B. The AGCT patients represented mother and daughter. Family C. The AGCT patients represented niece and aunt. Their mother, respectively sister was diagnosed with breast cancer. Patient C2 was involuntarily childless because of subfertility and more cases of subfertility were reported in this family. Family D. The AGCT patients were related through their grandfathers, who were brothers. Both mothers of the patients were diagnosed with breast cancer. One of the patient’s sisters was also involuntarily childless due to subfertility.
Figure 2
Figure 2
Filter approach.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020;70:7–30. doi: 10.3322/caac.21590. - DOI - PubMed
    1. Schumer S.T., Cannistra S.A. Granulosa cell tumor of the ovary. J. Clin. Oncol. 2003;21:1180–1189. doi: 10.1200/JCO.2003.10.019. - DOI - PubMed
    1. Gainder S., Kaur J., Siwatch S., Gupta N. Adult Granulosa Cell Tumor: A Sinister Differential for Clomiphene-resistant Infertility. J. Hum. Reprod. Sci. 2018;11:190–192. - PMC - PubMed
    1. Lappohn R.E., Burger H.G., Bouma J., Bangah M., Krans M., de Bruijn H.W. Inhibin as a marker for granulosa-cell tumors. N. Engl. J. Med. 1989;321:790–793. doi: 10.1056/NEJM198909213211204. - DOI - PubMed
    1. Karnezis A.N., Cho K.R., Gilks C.B., Pearce C.L., Huntsman D.G. The disparate origins of ovarian cancers: Pathogenesis and prevention strategies. Nat. Rev. Cancer. 2016;17:65–74. doi: 10.1038/nrc.2016.113. - DOI - PubMed

LinkOut - more resources