CHEK2p.I157T Mutation Is Associated with Increased Risk of Adult-Type Ovarian Granulosa Cell Tumors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F22%3A10443639" target="_blank" >RIV/00669806:_____/22:10443639 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11140/22:10443639

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SIf-LCPw3J" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SIf-LCPw3J</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers14051208" target="_blank" >10.3390/cancers14051208</a>

Result language

angličtina

Original language name

CHEK2p.I157T Mutation Is Associated with Increased Risk of Adult-Type Ovarian Granulosa Cell Tumors

Original language description

Simple Summary Granulosa cell tumors of the ovary represent a distinct subset of ovarian cancers typically characterized by hormonal disbalance, slow disease progression, and late recurrence years after surgical removal of the primary tumor. Risk factors associated with development of these rare tumors have not yet been established. In this study, we identified an association between increased risk of developing adult-type granulosa cell tumors (AGCTs) and a specific germline mutation in the CHEK2 gene. Our findings further support the relevance of this deleterious mutation in the increased risk of various cancer types, and opens a new avenue that can be exploited for future development of CHEK2-targeted preventive and therapeutic interventions directed at AGCTs. Pathogenic germline mutations c.1100delC and p.I157T in the CHEK2 gene have been associated with increased risk of breast, colon, kidney, prostate, and thyroid cancers; however, no associations have yet been identified between these two most common European founder mutations of the CHEK2 gene and ovarian cancers of any type. Our review of 78 female heterozygous carriers of these mutations (age &gt; 18 years) found strikingly higher proportion of adult-type granulosa cell tumors of the ovary (AGCTs) among ovarian cancers that developed in these women (~36%) compared to women from the general population (1.3%). Based on this finding, we performed a cross-sectional study that included 93 cases previously diagnosed with granulosa cell tumors, refined and validated their AGCT diagnosis through an IHC study, determined their status for the two CHEK2 mutations, and compared the prevalence of these mutations in the AGCT cases and reference populations. The prevalence ratios for the p.I157T mutation in the AGCT group relative to the global (PR = 26.52; CI95: 12.55-56.03) and European non-Finnish populations (PR = 24.55; CI95: 11.60-51.97) support an association between the CHEK2(p.I157T) mutation and AGCTs. These rare gynecologic tumors have not been previously associated with known risk factors and genetic predispositions. Furthermore, our results support the importance of the determination of the FOXL2(p.C134W) somatic mutation for accurate diagnosis of AGCTs and suggest a combination of IHC markers that can serve as a surrogate diagnostic marker to infer the mutational status of this FOXL2 allele.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30109 - Pathology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

2072-6694

Volume of the periodical

14

Issue of the periodical within the volume

5

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

1208

UT code for WoS article

000768122700001

EID of the result in the Scopus database

2-s2.0-85125191860