The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice
Ovarian cancer (OC) has the highest mortality rate of all gynaecological malignancies. The asymptomatic nature and limited understanding of early disease hamper research into early-stage OC. Therefore, there is an urgent need for models of early-stage OC to be characterised to improve the understand...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/9/2595 |
| _version_ | 1797602856499412992 |
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| author | Sarah Sczelecki Janet L. Pitman |
| author_facet | Sarah Sczelecki Janet L. Pitman |
| author_sort | Sarah Sczelecki |
| collection | DOAJ |
| description | Ovarian cancer (OC) has the highest mortality rate of all gynaecological malignancies. The asymptomatic nature and limited understanding of early disease hamper research into early-stage OC. Therefore, there is an urgent need for models of early-stage OC to be characterised to improve the understanding of early neoplastic transformations. This study sought to validate a unique mouse model for early OC development. The homozygous Fanconi anaemia complementation group D2 knock-out mice (<i>Fancd2<sup>−/−</sup></i>) develop multiple ovarian tumour phenotypes in a sequential manner as they age. Using immunohistochemistry, our group previously identified purported initiating precursor cells, termed ‘sex cords’, that are hypothesised to progress into epithelial OC in this model. To validate this hypothesis, the sex cords, tubulostromal adenomas and equivalent controls were isolated using laser capture microdissection for downstream multiplexed gene expression analyses using the Genome Lab GeXP Genetic Analysis System. Principal component analysis and unbiased hierarchical clustering of the resultant expression data from approximately 90 OC-related genes determined that cells from the sex cords and late-stage tumours clustered together, confirming the identity of the precursor lesion in this model. This study, therefore, provides a novel model for the investigation of initiating neoplastic events that can accelerate progress in understanding early OC. |
| first_indexed | 2024-03-11T04:22:26Z |
| format | Article |
| id | doaj.art-a112f70a1d30465a85cf01e0cbf39e0f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T04:22:26Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a112f70a1d30465a85cf01e0cbf39e0f2023-11-17T22:41:55ZengMDPI AGCancers2072-66942023-05-01159259510.3390/cancers15092595The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO MiceSarah Sczelecki0Janet L. Pitman1The School of Biological Sciences, Te Herenga Waka Victoria University of Wellington, Wellington 6012, New ZealandThe School of Biological Sciences, Te Herenga Waka Victoria University of Wellington, Wellington 6012, New ZealandOvarian cancer (OC) has the highest mortality rate of all gynaecological malignancies. The asymptomatic nature and limited understanding of early disease hamper research into early-stage OC. Therefore, there is an urgent need for models of early-stage OC to be characterised to improve the understanding of early neoplastic transformations. This study sought to validate a unique mouse model for early OC development. The homozygous Fanconi anaemia complementation group D2 knock-out mice (<i>Fancd2<sup>−/−</sup></i>) develop multiple ovarian tumour phenotypes in a sequential manner as they age. Using immunohistochemistry, our group previously identified purported initiating precursor cells, termed ‘sex cords’, that are hypothesised to progress into epithelial OC in this model. To validate this hypothesis, the sex cords, tubulostromal adenomas and equivalent controls were isolated using laser capture microdissection for downstream multiplexed gene expression analyses using the Genome Lab GeXP Genetic Analysis System. Principal component analysis and unbiased hierarchical clustering of the resultant expression data from approximately 90 OC-related genes determined that cells from the sex cords and late-stage tumours clustered together, confirming the identity of the precursor lesion in this model. This study, therefore, provides a novel model for the investigation of initiating neoplastic events that can accelerate progress in understanding early OC.https://www.mdpi.com/2072-6694/15/9/2595epithelial ovarian cancerprecursor lesionmouse model |
| spellingShingle | Sarah Sczelecki Janet L. Pitman The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice Cancers epithelial ovarian cancer precursor lesion mouse model |
| title | The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice |
| title_full | The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice |
| title_fullStr | The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice |
| title_full_unstemmed | The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice |
| title_short | The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in <i>Fancd2-</i>KO Mice |
| title_sort | validation of a precursor lesion of epithelial ovarian cancer in i fancd2 i ko mice |
| topic | epithelial ovarian cancer precursor lesion mouse model |
| url | https://www.mdpi.com/2072-6694/15/9/2595 |
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