? Cancer Res: Here's the latest insights into how ovarian cancer is evolving and evolving.

Highly liquid ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, accounting for 70-80% of ovarian cancer deaths, and is associated with poor prognostication and frequent recurrence.
HGS ovarian cancer is a complex genomic disease characterized by a widespread TP53 mutation, frequent loss of RB1, NF1 and PTEN due to gene fracture events, and recurrent high-level copy number amplification.
because of the complexity and wide heterogeneity of the disease, molecular stratation of HGSOC is very difficult.
Currently, clinically relevant genomic stratation is limited to the identification of isogenetic recombinant defects (HRD), a disease that accounts for about half of all HGS ovarian tumors and can be attributed to the lineage or soy cell BRCA mutations in about 20% of HGSOC cases.
studies have also reported different subsypes in molecules by grouping tumors with similar transcriptional groups.
Cancer Genome Map (TCGA) project reported four subtypes and named them after the expression of the labeled genes: differentiation, immune response, interstitrome and proliferation.
found that these subsypes are associated with several clinical and tumor pathological characteristics and may reflect tissues from different sources, in part reflecting differences in immune cell and substring content.
robustness and clinical practicality of the transcription group subtypes are still controversial.
based on the outline of 15 microarray datasets consisting of approximately 1,800 HGSOC tumors, subtype classifiers do not adapt well to independent data sets and divide only one-third of patients into four subtypes.
most HGSOC tumors are polyclonal, which means that individual tumors are heterogeneic assemblies of different cancer genotypes of different subsexuals.
estimates, 95 percent of TCGA HGSOC tumors are polyclonal, and about 40 percent are made up of four subclonals.
recent single-cell studies have further shown that HGS ovary tumors have a wide range of in-tumor heterogeneity, consistent with the concept that individual tumors are a mixture of different malignant cell groups.
the researchers hypothesically assume that subsexual distribution through transcription clustering is driven by late-stage events in tumor evolution, so these subspoles will be subclonal-specific.
first tested this hypothesis by identifying a genomic region of a new isologen-specific number of copies as a subtype marker in bulk tumors.
contrary to systematic developmental analysis based on longitudinal genome-wide sequencing at multiple points in time, this method infers tumor evolution at a single point in time from copy number data obtained from genotype array or exon group sequencing.
researchers analyzed single-cell RNA-seq (scRNA-seq) in six independent patients to see if individual skin cancer cells had different specific subtypes and whether they corresponded to the recommended large tumor subtypes.
, more than 20,000 women are diagnosed with new ovarian cancer each year, and about 14,000 die each year.
this paper has profound insights into each other's law and decades of tumor occurrence, and has basic scientific significance.
these insights are helpful to the feasibility of sub-targeted therapies.
it is difficult to understand the development of heterogeneity tumors before diagnosis because we cannot observe this change directly.
, however, researchers can still learn something by looking at tumors found at different stages of the evolutionary process, and by studying tumor genomics and heterogeneity in detail.
they wanted to know whether tumors would start in a subsype and stay in this way, or whether they would develop, change, or even multiply over time.
if subtypes can evolve and reproduce within a tumor, subtype-specific therapies are unlikely to help.
studies have identified transcriptional subtypes of advanced slurry ovarian cancer (HGSOC), but have not yet affected clinical practice.
interpretation and translation of HGSOC subtypes is complicated by the evolution and multiclosor nature of tumors and the accumulation of body malformations, mixtures of different cell types, and tissues from different sources.
Against the background of these factors, the chronological order of HGSOC subtype evolution was examined through a new comprehensive analysis of the number of absolute soyacyte copies and gene expression in the cancer genome map, as well as a single-cell RNA-seq analysis of six independent tumors.
this method compared to soft tissue sarcoma.
genomic lesions associated with HGSOC subsypes tend to be subclonal, which means late subsope dispersion in tumor evolution.
the recurrent subclonality of HGSOC is particularly evident in the growth of tumors, characterized by extreme genomic instability, lack of immuno-immersion and older patients.
, differentiated tumors are characterized by complete genomes, high immune penetration, and young patients.
researchers have proposed an alternative model of HGSOC discrete subtypes, where tumors develop from an early differentiated spectrum to a late-stage proliferation spectrum along a schedule characterized by genomic instability and the increase in subclonal amplification.
method proposed by the university provides a new method for studying tumor evolution through multi-histological analysis.
this study suggests a way to infer whether the transcription-based tumor group differentiates early in cancer and may therefore be a suitable target for treatment, and to prove that high-level slurry ovarian cancer (HGSOC) is not the case.
important findings of HGSOC include the reliable inference of tumor purity, multiply and subclonality from different genomic platforms and the display of significant differences between subtypes.
relapse DNA changes are associated with subtypes and tend to occur more frequently in subclonals where single-cell sequencing of 42,000 tumor cells shows that there is a wide range of heterogeneity in tumor cell type composition, which drives the call of a large number of subtypes, but indicates a lack of internal subtypes in tumor endoblast cells.
"We use complementary but completely different approaches to solving the same problem - one is to use a more traditional method of DNA and RNA sequencing of hundreds of large tumors, and the other is to use a new single-cell sequencing method for certain tumors," Waldron explains. The surprising result of the
study was the elimination of the idea of discrete transcription group subtypes of the cancer and the replacement of the model with a continuous tumor development model that included a mixture of subclonals, the accumulation of mutations, immune and substring cells in a tumor-related ratio of immersion stages and tissue origin, and evolution between previous characteristics associated with discrete subtypes.
the study, researchers investigated whether HGSOC subsypes based on gene expression were due to inherent ambiguity at the level of individual tumor cells or subclonal mixtures of subsypes defined differently.
Although subtype-related DNA changes tend to occur more frequently in subclonals, the researchers found that this was due only to the overall higher multiplility and subclonality of proliferating spectral tumors, rather than to the existence of subclonals with different definitive subtypes.
on the other hand, subtype classification of individual cells suggests that the difference is due to a combination of (i) a mixture of a large number of cell types and (ii) characteristics from one subtype to another.
from these observations, the concept of discrete subtypes does not actually represent the heterogeneity and genomic complexity of HGSOC.
, the researchers suggest that HGSOC is characterized by heterogeneity, which is determined primarily by the evolution and composition of tumors.
In this model, tumors are caused by random and individual genome changes (caused by a limited set of evolutionary movements) from a largely complete genome (an early differentiation spectrum) to a complete loss of genomic integrity (post-proliferation spectrum), resulting in increased genomic instability and subclonal amplification.
Together with tumor purity and heterogeneity of composition, the tumor is assigned to immune reactive and interstitrome mass spectrometrometromety, which provides an explanation for the ambiguity of subtype classification, which also exists at the cellular level and even exceeds the classification ambiguity of large tumors.
to use human samples for experimental validation of the model, as it is not feasible to collect longitudinal samples from patients as tumors develop.
longitudinal samples can be obtained from genetically modified mice developing ovarian cancer.
Because of the close relationship between the patient's age and HGSOC's tumor stages, this also means that the earlier stage may be at least partly due to earlier discoveries rather than more stubborn tumors, and that this stage may have developed for decades.
with more single-celled data for HGSOC available in the near future, it will be possible to study tumors more fully before, during and after the critical transition period.
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