Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

Kim, Susan; Woo, Ha Young; Im, Sung Il; Kim, Hyunsoo

doi:10.21873/invivo.11628

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…DNA and RNA were quantified using the Qubit 2.0 Fluorometer (Thermo Fisher Scientific). DNA and RNA libraries were prepared as previously described (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). These DNA libraries were generated from 20 ng of DNA per sample using an Ion AmpliSeq Library Kit 2.0 (Thermo Fisher Scientific) and the Oncomine Comprehensive Assay v1 (OCA v1) panel (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Yoon

Kim

Lee

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Glioblastoma is the most malignant form of astrocytoma. The purpose of this study was to analyze the genetic characteristics of primary and recurrent glioblastomas using targeted sequencing and investigate the differences in mutational profiles between the locations of tumor recurrence. Materials and Methods: Fourteen glioblastoma patients who developed local (n=10) or distal (n=4) recurrence were included in the study. Targeted sequencing analysis was performed using the primary (n=14) and corresponding recurrent (n=14) tumor tissue samples. Results: The local and distal recurrence groups showed different genetic evolutionary patterns. Most of the locally recurrent glioblastomas demonstrated concordant mutational profiles between the primary and recurrent tumors, suggesting a linear evolution. In contrast, all cases of distally recurrent glioblastomas showed changes in mutational profiles with newly acquired mutations when compared to the corresponding primary tumors, suggesting a branching evolution. Conclusion: Locally and distally recurrent glioblastomas exhibit different evolutionary patterns. Glioblastoma is the most common malignant tumor of the central nervous system (1-9). The current standard treatment for glioblastoma involves surgical resection, followed by concurrent chemoradiation therapy and adjuvant chemotherapy using temozolomide (8-12). Due to the invasive nature of glioblastoma, surgical resection rarely eliminates all tumor cells, and postoperative treatment is usually necessary to prevent disease recurrence. Despite the advances made in therapeutic strategies, the prognosis of patients with glioblastoma remains very poor, with an average survival of 15 months (13-15) and disease recurrence being the major cause of mortality (16-18). Recurrent glioblastomas tend to be more invasive and resistant to chemotherapy than primary tumors. An understanding of the genetic characteristics of recurrent glioblastoma is crucial for identifying potential targets for drug discovery, stratifying patients for diagnosis, and optimizing an effective treatment strategy. Previous studies have shown the molecular features of recurrent glioblastomas. In particular, the mutational profiles observed in recurrent glioblastomas were compared to those of the corresponding primary tumors (19-21). However, there is a lack of studies exploring the differences in mutational profiles between recurrent glioblastomas at different sites (21, 22). In this study, we investigated the mutational profiles of primary and recurrent glioblastomas using 803 This article is freely accessible online.

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Section: Methodsmentioning

confidence: 99%

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Yoon

Kim

Lee

et al. 2020

Cancer Genomics Proteomics

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“…Based on the TCGA dataset, the most frequent types of TP53 variations in HGSC are missense (60.52%), followed by frameshift (15.24%), nonsense (10.73%), splice site (10.52%), and in-frame mutations (3.22%) [13] 1). Interestingly, while many driver mutations evolved in response to treatment leading to treatment resistance [82], TP53 mutations remain unchanged during the course of the disease [83].…”

Section: Tp53 Mutations In Hgsc and Their Clinical Relevancementioning

confidence: 99%

“…A total of 126/282 (44.68%) hotspot mutations were observed in HGSC according to the TCGA, with the nine most common ones being: R273 (20.63%, 26/126), R248 (16.67%, 21/126), R175 (14.29%, 18/126), Y220 (9.52%, 12/126), I195 (9.52%, 12/126), C176 (8.73%, 11/126), G245 (8.73, 11/126), S241 (6.35%, 8/126), and Y163 (6.35%, 8/126) [ 23 ] ( Figure 1 ). Interestingly, while many driver mutations evolved in response to treatment leading to treatment resistance [ 82 ], TP53 mutations remain unchanged during the course of the disease [ 83 ].…”

Section: Tp53 Mutations In Hgsc and Their Clinical Relevancementioning

confidence: 99%

Mutated p53 in HGSC—From a Common Mutation to a Target for Therapy

Saleh

Perets

2021

Cancers

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Mutations in tumor suppressor gene TP53, encoding for the p53 protein, are the most ubiquitous genetic variation in human ovarian HGSC, the most prevalent and lethal histologic subtype of epithelial ovarian cancer (EOC). The majority of TP53 mutations are missense mutations, leading to loss of tumor suppressive function of p53 and gain of new oncogenic functions. This review presents the clinical relevance of TP53 mutations in HGSC, elaborating on several recently identified upstream regulators of mutant p53 that control its expression and downstream target genes that mediate its roles in the disease. TP53 mutations are the earliest genetic alterations during HGSC pathogenesis, and we summarize current information related to p53 function in the pathogenesis of HGSC. The role of p53 is cell autonomous, and in the interaction between cancer cells and its microenvironment. We discuss the reduction in p53 expression levels in tumor associated fibroblasts that promotes cancer progression, and the role of mutated p53 in the interaction between the tumor and its microenvironment. Lastly, we discuss the potential of TP53 mutations to serve as diagnostic biomarkers and detail some more advanced efforts to use mutated p53 as a therapeutic target in HGSC.

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“…Immunostaining was performed using a compact polymer method (Bond Polymer Refine Detection kit, Leica Biosystems, Newcastle, United Kingdom) [ 13 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The tumor cells showed focal nuclear PAX2 immunoreactivity with mild-to-moderate staining intensity ( Figure 2 A).…”

Section: Case Presentationmentioning

confidence: 99%

Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation

2021

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We present herein a rare case of uterine serous carcinoma with mesonephric-like differentiation (SC-MLD) initially misdiagnosed as mesonephric-like adenocarcinoma (MLA). A 51-year-old woman underwent total hysterectomy for a uterine tumor. Histologically, the tumor exhibited various architectures, including papillary, glandular, tubular, cribriform, and cystic. On the basis of this architectural diversity accompanied by intraluminal eosinophilic secretions and intermediate-grade nuclear atypia, the initial diagnosis was MLA. However, the tumor was diffusely and strongly positive for the expression of p16 and negative for the expression of GATA-binding protein 3 (GATA3). Furthermore, we identified a pathogenic tumor protein 53 (TP53) mutation affecting an acceptor splice site in intron 9, despite a wild-type p53 immunostaining pattern. The observations of diffuse and strong p16 expression, lack of GATA3 expression, pathogenic TP53 mutation, and wild-type Kirsten rat sarcoma viral oncogene homolog indicate that this tumor was not an MLA but an SC-MLD. Both uterine SC and MLA can exhibit various histological growth patterns. Our comprehensive clinicopathological and molecular analyses can serve to improve the understanding of this rare condition and help pathologists in making an accurate diagnosis.

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Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

Cited by 8 publications

References 42 publications

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Mutated p53 in HGSC—From a Common Mutation to a Target for Therapy

Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation

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