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Cancers
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Genomic Characterization of Gynecological Cancer
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Genomic Characterization of Gynecological Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (20 November 2023) | Viewed by 6314

Special Issue Editors

Dr. Gulisa Turashvili

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
Interests: breast cancer; gynecologic cancers; breast pathology; gynecologic pathology
Special Issues, Collections and Topics in MDPI journals
Dr. Amir Momeni-Boroujeni

E-Mail Website
Guest Editor
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Interests: ovarian cancer; endometrial cancer; uterine mesenchymal tumors; cervical cancer; vulvar cancer

Special Issue Information

Dear Colleagues,  

Over the past decade, integrated genomic analysis of gynecologic cancers has unraveled characteristic molecular alterations, including driving mutations, gene fusions and amplifications. Many of these alterations can be used for diagnostic, prognostic or predictive purposes in different types of epithelial and mesenchymal neoplasms. Some of the important examples are the Cancer Genome Atlas (TCGA) classification of endometrial carcinoma, homologous recombination deficiency in high-grade serous carcinomas, and BCOR and other gene fusions in endometrial stromal sarcomas, among others. These genetic abnormalities have tremendous potential to ensure accurate diagnosis with optimal clinical management and avoid over- or undertreatment.  

In this Special Issue, we welcome contributions from both scientists and health care professionals such as medical oncologists, surgical oncologists, radiation oncologists, pathologists, radiologists, and geneticists. Either original research articles or comprehensive reviews will be considered. Specific topics related to gynecologic neoplasms may include, but are not limited to, the following: molecular pathways; new and emerging diagnostic, prognostic or therapeutic targets; novel therapeutics, including immunotherapeutic approaches. We look forward to receiving your contributions.  

Dr. Gulisa Turashvili
Dr. Amir Momeni-Boroujeni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancer
  • endometrial cancer
  • uterine mesenchymal tumors
  • cervical cancer
  • genomic characterization

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Published Papers (3 papers)

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Research

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19 pages, 5367 KiB  
Article
Genomic Landscape of Endometrial, Ovarian, and Cervical Cancers in Japan from the Database in the Center for Cancer Genomics and Advanced Therapeutics
by Qian Xi, Hidenori Kage, Miho Ogawa, Asami Matsunaga, Akira Nishijima, Kenbun Sone, Kei Kawana and Katsutoshi Oda
Cancers 2024, 16(1), 136; https://doi.org/10.3390/cancers16010136 - 27 Dec 2023
Cited by 5 | Viewed by 1995
Abstract
This study aimed to comprehensively clarify the genomic landscape and its association with tumor mutational burden-high (TMB-H, ≥10 mut/Mb) and microsatellite instability-high (MSI-H) in endometrial, cervical, and ovarian cancers. We obtained genomic datasets of a comprehensive genomic profiling test, FoundationOne® CDx, with [...] Read more.
This study aimed to comprehensively clarify the genomic landscape and its association with tumor mutational burden-high (TMB-H, ≥10 mut/Mb) and microsatellite instability-high (MSI-H) in endometrial, cervical, and ovarian cancers. We obtained genomic datasets of a comprehensive genomic profiling test, FoundationOne® CDx, with clinical information using the “Center for Cancer Genomics and Advanced Therapeutics” (C-CAT) database in Japan. Patients can undergo the tests only after standardized treatments under universal health insurance coverage. Endometrial cancers were characterized by a high frequency of TMB-H and MSI-H, especially in endometrioid carcinomas. The lower ratio of POLE exonuclease mutations and the higher ratio of TP53 mutations compared to previous reports suggested the prognostic effects of the molecular subtypes. Among the 839 cervical cancer samples, frequent mutations of KRAS, TP53, PIK3CA, STK11, CDKN2A, and ERBB2 were observed in adenocarcinomas, whereas the ratio of TMB-H was significantly higher in squamous cell carcinomas. Among the 1606 ovarian cancer samples, genomic profiling of serous, clear cell, endometrioid, and mucinous carcinomas was characterized. Pathogenic mutations in the POLE exonuclease domain were associated with high TMB, and the mutation ratio was low in both cervical and ovarian cancers. The C-CAT database is useful for determining the mutational landscape of each cancer type and histological subtype. As the dataset is exclusively collected from patients after the standardized treatments, the information on “druggable” alterations highlights the unmet needs for drug development in major gynecological cancers. Full article
(This article belongs to the Special Issue Genomic Characterization of Gynecological Cancer)
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17 pages, 3762 KiB  
Article
WNT4 Gene and Protein Expression in Endometrial Cancer and Its Significance
by Jolanta Kiewisz, Tomasz Waśniewski, Jacek Kieżun, Agnieszka Skowrońska, Monika M. Kaczmarek, Błażej Szóstak, Anna E. Kowalczyk and Zbigniew Kmieć
Cancers 2023, 15(19), 4780; https://doi.org/10.3390/cancers15194780 - 28 Sep 2023
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Abstract
Background: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). Objective: The aim was to evaluate the alterations of WNT4 gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the [...] Read more.
Background: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). Objective: The aim was to evaluate the alterations of WNT4 gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. Methods: WNT4 mRNA levels were compared between benign (control) endometrium (n = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (n = 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC). WNT4 mRNA gene and WNT4-Ir were correlated with clinicopathological and blood morphological parameters. Overall survival (OS) was assessed. The bioanalysis was utilized to study WNT4 expression in large patient cohort (n = 549). Results: WNT4 gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The WNT4 gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS and WNT4 gene expression and WNT4-Ir. Bioanalysis showed that WNT4 and ESR1 gene expression alterations tended to be mutually exclusive. An alteration in WNT4 expression was found in different histological tumor types in a large group of EC patients. Conclusions: There is a great need to evaluate the molecular background of EC. Our study suggests that the WNT4 gene has the potential to be a marker of functional estrogen signaling in EEC. Full article
(This article belongs to the Special Issue Genomic Characterization of Gynecological Cancer)
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Review

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43 pages, 20536 KiB  
Review
Relevance of Molecular Pathology for the Diagnosis of Sex Cord–Stromal Tumors of the Ovary: A Narrative Review
by Alexis Trecourt, Marie Donzel, Nadjla Alsadoun, Fabienne Allias and Mojgan Devouassoux-Shisheboran
Cancers 2023, 15(24), 5864; https://doi.org/10.3390/cancers15245864 - 15 Dec 2023
Cited by 5 | Viewed by 2222
Abstract
Ovarian sex cord–stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant [...] Read more.
Ovarian sex cord–stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as FOXL2 variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz–Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli–Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the DICER1 variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature. Full article
(This article belongs to the Special Issue Genomic Characterization of Gynecological Cancer)
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