A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations

Stružinská, Ivana; Hájková, Nikola; Hojný, J.; Krkavcová, Eva; Michálková, Romana; Dvořák, Jiří; Němejcová, Kristýna; Matěj, Radoslav; Laco, Ján; Drozenová, Jana; Fabián, Pavel; Hausnerová, Jitka; Méhes, Gábor; Škapa, Petr; Švajdler, Marián; Cibula, David; Frühauf, F.; Bártů, Michaela; Dundr, Pavel

doi:10.1186/s13000-023-01358-0

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…Buparlisib targets the PI3K/Akt pathway and holds potential for therapeutic intervention in HSCC [ 13 ]. AKT2, AKT3, and PTEN could also exert influences on regulating multiple microenvironment-related factors that are associated with chemosensitivity, including drug metabolism, DNA repair, cell cycle regulation, inflammatory responses, and cellular signaling pathways, all contributing to chemosensitivity [ 14 – 18 ]. These findings suggest that targeting the PI3K/Akt pathway with modulating agents like buparlisib may be a promising strategy for HSCC treatment, potentially improving patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma

Han,

Chen,

Chen

et al. 2024

PPAR Research

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It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (p<0.04) of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (p=0.01), while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (p≤0.04). Positive correlations (R∈0.43,0.71, p<0.014) were observed between PIK3CA, AKT1, AKT2, AKT3, and PTEN, with AKT2, AKT3, and PTEN also showing significant correlations with PPARG (R∈0.35,0.47, p<0.04). Age, gender, and disease stage had no influence on PPARG, PIK3CA, and PTEN expression, but they may affect AKT expressions. Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients.

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Section: Discussionmentioning

confidence: 99%

PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma

Han,

Chen,

Chen

et al. 2024

PPAR Research

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“…Transcriptome RNA-Seq libraries were constructed using KAPA RNA HyperPrep Kit according to the Roche KAPA HyperCap Workflow v3.2 with minor modifications (RNA fragmentation 65°C for 2 min; KAPA UMI adapters were used at a final concentration of 750 nM; total 13 PCR cycles using KAPA UDI Primer Mixes). Exome DNA libraries from tumor tissue only were prepared using KAPA HyperExome probes (Roche) by KAPA HyperCap Workflow v3.2 as described before [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…Bioinformatic analysis of raw sequencing data, genomic variants annotation, tumor mutation burden (TMB) calculation, and fusion detection was processed as described before [ 19 ]. Tumor vs paired non-tumor tissue differential expression analysis was performed using the Differential Expression in Two Groups module in CLC Genomics Workbench v23.0.2 software (CLC GW; Qiagen).…”

Section: Methodsmentioning

confidence: 99%

Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases

et al. 2023

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Three main uterine leiomyoma molecular subtypes include tumors with MED12 mutation, molecular aberrations leading to HMGA2 overexpression, and biallelic loss of FH. These aberrations are mutually exclusive and can be found in approximately 80–90% of uterine leiomyoma, in which they seem to be a driver event. Approximately 10% of uterine leiomyoma, however, does not belong to any of these categories. Uterine leiomyoma with HMGA2 overexpression is the most common subtype in cellular and second most common category of usual leiomyoma. In some of these tumors, rearrangement of HMGA2 gene is present. The most common fusion partner of HMGA2 gene is RAD51B. Limited data suggests that RAD51B fusions with other genes may be present in uterine leiomyoma. In our study, we described two cases of uterine leiomyoma with RAD51B::NUDT3 fusion, which occur in one case of usual and one case of highly cellular leiomyoma. In both cases, no other driver molecular aberrations were found. The results of our study showed that RAD51::NUDT3 fusion can occur in both usual and cellular leiomyoma. RAD51B may be a fusion partner of multiple genes other than HMGA2 and HMGA1. In these cases, RAD51B fusion seems to be mutually exclusive with other driver aberrations defining molecular leiomyoma subtypes. RAD51B::NUDT3 fusion should be added to the spectrum of fusions which may occur in uterine leiomyoma, which can be of value especially in cellular leiomyoma in the context of differential diagnosis against endometrial stromal tumors.

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“…In diagnostics, most RNA capture-based NGS has been limited to analysing a few dozen genes (Davy et al, 2017;Karam et al, 2020;Horton et al, 2022Horton et al, , 2024. RNA capture-based NGS covering hundreds of genes is more commonly used for research purposes only (Hojny et al, 2022;Struzinska et al, 2023). It could not only precisely identify alternative splicing events in a tissuespecific manner but also assess the effect of DNA variants on the pre-mRNA splicing (Davy et al, 2017;Farber-Katz et al, 2018;Lattimore et al, 2018Lattimore et al, , 2019Brandão et al, 2019;Lopez-Perolio et al, 2019;Walker et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Parallel DNA/RNA NGS Using an Identical Target Enrichment Panel in the Analysis of Hereditary Cancer Predisposition

Kleiblová,

Černá,

Zemánková

et al. 2024

Fol. Biol.

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Germline DNA testing using the next-generation sequencing (NGS) technology has become the analytical standard for the diagnostics of hereditary diseases, including cancer. Its increasing use places high demands on correct sample identification, independent confirmation of prioritized variants, and their functional and clinical interpretation. To streamline these processes, we introduced parallel DNA and RNA capture-based NGS using identical capture panel CZECANCA, which is routinely used for DNA analysis of hereditary cancer predisposition. Here, we present the analytical workflow for RNA sample processing and its analytical and diagnostic performance. Parallel DNA/RNA analysis allowed credible sample identification by calculating the kinship coefficient. The RNA capture-based approach enriched transcriptional targets for the majority of clinically relevant cancer predisposition genes to a degree that allowed analysis of the effect of identified DNA variants on mRNA processing. By comparing the panel and whole-exome RNA enrichment, we demonstrated that the tissue-specific gene expression pattern is independent of the capture panel. Moreover, technical replicates confirmed high reproducibility of the tested RNA analysis. We concluded that parallel DNA/RNA NGS using the identical gene panel is a robust and cost-effective diagnostic strategy. In our setting, it allows routine analysis of 48 DNA/RNA pairs using NextSeq 500/550 Mid Output Kit v2.5 (150 cycles) in a single run with sufficient coverage to analyse 226 cancer predisposition and candidate genes. This approach can replace laborious Sanger confirmatory sequencing, increase testing turnaround, reduce analysis costs, and improve interpretation of the impact of variants by analysing their effect on mRNA processing.

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A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations

Cited by 4 publications

References 37 publications

PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma

PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma

Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases

Parallel DNA/RNA NGS Using an Identical Target Enrichment Panel in the Analysis of Hereditary Cancer Predisposition

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