scholarly journals Molecular genetic classification of colorectal cancer subtypes: current state of the problem

2021 ◽  
Vol 2 (2) ◽  
pp. 50-56
Author(s):  
O. I. Kit ◽  
E. A. Dzhenkova ◽  
E. A. Mirzoyan ◽  
Yu. A. Gevorkyan ◽  
A. B. Sagakyants ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Genetic ◽  
Response To Therapy ◽  
Diagnostic Methods ◽  
Genetic Classification ◽  
Genetic Changes ◽  
Genetic Characteristics ◽  
Cancer Subtypes ◽  
Methylator Phenotype ◽  
Diagnostic Capabilities

Today, colorectal cancer (CRC) is the third most common cancer and therefore an urgent problem of oncology. Despite all modern diagnostic capabilities, the rates of advanced cases are growing steadily. CRC was proven to be a result of a phased dysplastic change in the colon mucosa, molecular genetic changes that determine the molecular biology of the tumor, its properties, morphology, disease prognosis and response to therapy. The following mechanisms of CRC tumor progression are distinguished: chromosomal instability, microsatellite instability, "methylator" phenotype, and serrated pathway of adenocarcinoma development. Application of molecular and diagnostic methods has become a promising direction in recent years. This led to the development of a molecular genetic classifi cation with 4 CRC subtypes differing not only in their molecular genetic characteristics, but also in clinical course and response to therapy.

scholarly journals DIAGNOSTICS, TREATMENT AND PROGNOSIS IN PATIENTS WITH COLORECTAL CANCER AND PERITONEAL CARCINOMATOSIS (review)

2020 ◽  
Vol 19 (4) ◽  
pp. 131-149
Author(s):  
M. Yu. Fedyanin ◽  
A. A. Tryakin ◽  
M. D. Ter-Ovanesov ◽  
S. A. Tyulyandin
Keyword(s):  
Colorectal Cancer ◽  
Literature Review ◽  
Peritoneal Carcinomatosis ◽  
Systemic Therapy ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Specific Treatment ◽  
Peritoneal Metastases ◽  
Diagnostic Methods ◽  
Genetic Characteristics

Isolated colorectal peritoneal metastases occur in 1.8% of patients. This type of tumor is characterized by certain phenotypic and molecular genetic characteristics, which determines the choice of specific treatment options. In this literature review, along with a description of the main principles of the pathogenesis of the disease, the sensitivity and specificity of various diagnostic methods for colorectal peritoneal lesions, the choice of systemic therapy, the need to perform peritonectomy and Intraperitoneal hyperthermic chemoperfusionare considered.

The role of combined treatment of metastatic colorectal cancer inpatients with liver metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16026-e16026
Author(s):  
Mikhail Trandofilov ◽  
Danila Gridnev ◽  
Anatoly Popov ◽  
Anna Sizova ◽  
Dina Islamova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Metastatic Colorectal Cancer ◽  
Molecular Genetic ◽  
Combined Treatment ◽  
Surgical Techniques ◽  
Genetic Characteristics ◽  
Complex Therapy ◽  
Group A ◽  
Group B

e16026 Background: Combined treatment for patients with metastatic colorectal cancer (mCRC) offers better long-term outcomes and chemotherapy can increase the rate of hepatic resectability for patients with initially inoperable disease. Methods: The analysis included 132 patients diagnosed with mCRC having metastases in the liver treated from 2015 to 2020. Of these, 62 (47%) were men and 70 (53%) women. The average age of the patients was 63 years. At the beginning of the treatment, the overall condition of all patients met ECOG 0-1 points. Primary metastatic CRC had 93 (71%) patients. A total of 39 (29%) patients were diagnosed with advanced disease. Localization of the primary tumor in 25 patients (18.9%) was in the right part of the large intestine and 107 (81.1%) in the left part of the colon. At the time of the sample, metastases were detected only in the liver in 73 patients (55.3%). In the remaining 59 (44.7%) other organs were affected besides the liver. Various types of surgical treatment of metastases in the liver received 42 (31.8%) patients. The decision on the choice of chemotherapy was made by the attending physician on the basis of the recommendations of NCCN and RUSSCO, taking into account the molecular genetic characteristics of the tumor. The decision to apply and choose the method of surgical treatment was taken in conjunction with the surgeon. Results: From the general population of patients receiving complex therapy, 2 groups were identified, between which a comparison was made. The first group (group A) was 42 (31.8%) patients who received some surgical treatment of the liver. The second group (group B) included 90 (68.2%) patients, who for some reason or another, did not receive any surgical treatment. The groups are fairly homogeneous in their characteristics. The median overall survival (OS) in group A was 40.1 months, and in group B, 22.3 months. A similar trend continued in subgroup analysis. The calculation of the PFS was complicated by the fact that surgical operations were given at different stages of complex treatment. Three-year survival in group A was approximately 50%, and in group B, 28%. "Five-year" survival (In those patients who were observed from the start of the study for all 5 years) in group A was 15 %, and in group B, 5,5%. Conclusions: The inclusion of modern surgical techniques in the complex therapy of metastatic colorectal cancer, if possible, at any stage, can significantly increase the life expectancy of patients.

scholarly journals Retrospective study of prognosis of patients with multiple colorectal carcinomas: synchronous versus metachronous makes the difference

2021 ◽  
Author(s):  
Christoph Barz ◽  
Christian Stöss ◽  
Philipp-Alexander Neumann ◽  
Dirk Wilhelm ◽  
Klaus-Peter Janssen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Retrospective Analysis ◽  
Molecular Genetic ◽  
Survival Rates ◽  
Multivariable Analysis ◽  
Genetic Characteristics ◽  
Tertiary Referral Center ◽  
Tumor Stages ◽  
The Difference ◽  
Cause Specific Survival

Abstract Purpose Little is known about difference between synchronous colorectal cancer (SCRC) and metachronous colorectal cancer (MCRC) despite the relevance for this selected patient group. The aim of this retrospective review was to analyze patients with SCRC and MCRC. Methods All patients who underwent surgery for SCRC and MCRC between 1982 and 2019 were included in this retrospective analysis of our tertiary referral center. Clinical, histological, and molecular genetic characteristics were analyzed. The primary endpoint was cause-specific survival, evaluated by the Kaplan-Meier method. Secondary endpoints were recurrence-free survival and the identification of prognostic factors. Results Overall, 3714 patients were included in this analysis. Of those, 3506 (94.4%) had a primary unifocal colorectal cancer (PCRC), 103 (2.7%) had SCRC, and 105 (2.8%) had MCRC. SCRC occurred more frequently in elderly (p=0.009) and in male patients (p=0.027). There were no differences concerning tumor stages or grading. Patients with SCRC did not show altered recurrence or survival rates, as compared to unifocal tumors. However, MCRC had a lower rate of recurrence, compared to PCRC (24% vs. 41%, p=0.002) and a lower rate of cause-specific death (13% vs. 37%, p<0.001). Five-year cause-specific survival rates were 63±1% for PCRC, 62±6% for SCRC (p=0.588), and 88±4% for MCRC (p<0.001). Multivariable analysis revealed that MCRC were an independent favorable prognostic parameter regarding case-specific survival. Conclusion Patients with SCRC seem to not have a worse prognosis compared to patients with PCRC. Noteworthy, patients with MCRC showed better survival rates in this retrospective analysis.

scholarly journals Modern aspects of morphology of endometrial cancer and neuroendocrine tumors (to the 100th anniversary of the birth of O.K. Khmelnitsky)

2021 ◽  
Vol 102 (4) ◽  
pp. 581-586
Author(s):  
E M Nepomnyashchaya ◽  
T I Moiseenko ◽  
V S Trifanov
Keyword(s):  
Endometrial Cancer ◽  
Neuroendocrine Tumors ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Morphological Characteristics ◽  
100Th Anniversary ◽  
Medical Sciences ◽  
Genetic Classification ◽  
Genetic Changes

November 4, 2020, marks the 100th anniversary of the birth of Oleg Konstantinovich Khmelnitskiy, an outstanding Russian pathologist, Corresponding Member of the Russian Academy of Medical Sciences (04.11.192008.02.2004). The creative legacy of O.K. Khmelnitskiy has a large number of works devoted to endometrial cancer and neuroendocrine tumors. Modern concepts of these tumors take a lot from the scientists ideas. The development of the classification of endometrioid carcinomas is determined by new data in molecular genetic research. The most common genetic changes in endometrioid adenocarcinomas involve mutations in the PTEN, KRAS, CTNNB1, PIK3CA, and MS1 genes. Serous carcinomas are characterized by TP53 mutations and HER2-neu gene amplification. The immunohistochemical panel allows differentiation of endometrioid and serous carcinomas. There is evidence of the role of the POLE gene mutation. Various advantages of the introduction of molecular genetic classification are presented, which allow changing approaches to the treatment of endometrial cancer depending on the risk of its development. The 2019 neuroendocrine tumors (NETs) classification allows interpreting morphological characteristics of these tumors in a new way.

Use of colorectal cancer subtypes identified through iterative clustering to predict response to therapy.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 482-482
Author(s):  
Andreas Schlicker ◽  
Garry Beran ◽  
Christine M Chresta ◽  
Gael McWalter ◽  
Alison Pritchard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Expression Pattern ◽  
Therapy Response ◽  
Response To Therapy ◽  
Cancer Subtypes ◽  
Treatment Regimens ◽  
Genome Wide

482 Background: Colorectal cancer (CRC) is generally stratified based on genetic and epigenetic features, such as KRAS mutation and microsatellite instability status. In order to facilitate the development of new targeted drugs and treatment regimens, it is important to redefine CRC at the molecular level by identifying subtypes that are relevant for response to targeted therapy. Methods: We applied a new unsupervised approach for iteratively stratifying tumor samples using genome-wide mRNA expression data. The resulting gene expression signatures were used to subtype CRC cell line panels and publicly available CRC tumor datasets. We employed pharmacological data on the cell line panels to link the subtypes to therapy response. Results: Starting from a gene expression dataset of 63 CRC tumor samples, we employed non-negative matrix factorization (NMF) and identified two dominant CRC subtypes. In agreement with previously published results, one of the types showed a mesenchymal and the other an epithelial-like gene expression pattern. In a second step, we applied NMF on these two dominant subtypes and further stratified them into two and three subtypes, respectively. The resulting five CRC subtypes show many differences, most notably activation of specific signaling pathways. Importantly, we recovered these five subtypes in several independent, publicly available CRC datasets. This strongly suggests that the signatures capture disease-relevant features of CRC. Furthermore, we found that the different subtypes corresponded to different cell lines in a panel of CRC cell lines. The clustered CRC cell lines displayed differential responses to a number of targeted compounds, indicating that the new CRC clusters may represent disease subtypes that of differential drug sensitivity. Conclusions: The CRC subtypes discovered using our new method offer new insights into the functional and molecular processes driving CRC. Furthermore, the evidence suggests that these subtypes may differ in activated pathway status and the response to some targeted inhibitors, indicating that targeting pathways conserved in these subtypes may provide new drug discovery opportunities.

scholarly journals Analysis of platelet RNA: a non-invasive method for studying the expression of tumor genes

2021 ◽  
Vol 20 (1) ◽  
pp. 207-217
Author(s):  
I. P. Tesakov ◽  
A. A. Martyanov ◽  
A. E. Drui ◽  
A. N. Sveshnikova
Keyword(s):  
Clinical Practice ◽  
Tumor Cells ◽  
Molecular Genetic ◽  
Cancer Diagnostics ◽  
Response To Therapy ◽  
Genetic Characteristics ◽  
Non Invasive ◽  
Wide Range ◽  
Oncological Diseases ◽  
Invasive Method

Nowadays much attention is paid to non-invasive methods of cancer diagnostics and monitoring. One of the promising methods is the sequencing of platelet RNA (tumor-educated platelets), in which, as it was previously established, the mRNA repertoire changes in various oncological diseases. Thus, platelets can contain information about the molecular genetic characteristics of tumor. This review summarizes the current understanding of the mechanisms of interaction between tumor cells and platelets, and also discusses the possibilities of using platelet transcriptome analysis methods for diagnosing and assessing the dynamics of the tumor state, in particular, in response to therapy, as well as the current limitations for a wide range of introduction of this method into clinical practice. 

scholarly journals Molecular Genetic Characteristics of Colorectal Cancer in Patients 90 Years and Older Differ from the Findings in Younger Patients

2018 ◽  
Vol 6 (1) ◽  
pp. 510-515
Author(s):  
Peter Zauber ◽  
◽  
Rachna Kapoor ◽  
Stephen Marotta ◽  
Marlene Sabbath-Solitare
Keyword(s):  
Colorectal Cancer ◽  
Molecular Genetic ◽  
Genetic Characteristics ◽  
Younger Patients

scholarly journals Új molekuláris klasszifikációs rendszerek diffúz nagy B-sejtes limfómában

2021 ◽  
Vol 54 (2) ◽  
pp. 104-112
Author(s):  
Laura Kiss ◽  
Bence Bátai ◽  
Csaba Bödör ◽  
Ákos Nagy
Keyword(s):  
B Cell ◽  
Molecular Genetic ◽  
B Cell Lymphoma ◽  
Classification Systems ◽  
Diagnostic Methods ◽  
Molecular Diagnostic ◽  
Molecular Heterogeneity ◽  
Cell Of Origin ◽  
Genetic Classification ◽  
Wide Range

Összefoglaló. A diffúz nagy B-sejtes limfóma (DLBCL) a leggyakoribb non-Hodgkin-limfóma (NHL), az összes NHL-es eset mintegy 40%-a tartozik ide. A betegek kétharmada az első vonalbeli kemoimmunterápia hatására meggyógyul, azonban harmaduknál rendkívül agresszív DLBCL alakul ki. A rendelkezésre álló új terápiás lehetőségek ellenére a kemoimmunterápiára rosszul reagáló csoportban a terápiás siker egyelőre várat magára, aminek hátterében a betegség rendkívüli heterogenitása és ebből következően a klinikai vizsgálatokba történő nem megfelelő betegszelekció állhat. A jelenleg alkalmazott DLBCL besorolás a génexpresszió alapján meghatározott sejteredetnek megfelelően három csoportot különít el: a csíracentrum-eredetű (GCB), az aktivált B-sejt-eredetű (ABC) és a nem klasszifikálható DLBCL-es eseteket. Bár a GCB csoportba tartozó eseteknek jellemzően kedvezőbb a kórlefolyása, mint az ABC csoportba tartozóké, az egyes csoportokon belül továbbra is rendkívül sokszínű a várható kórlefolyás. A molekuláris diagnosztikai módszerek utóbbi évtizedekben látott fejlődésének köszönhetően olyan molekuláris eltérésekre derült fény, melyek egy új klasszifikációs rendszer alapköveiként szolgálhatnak. Az új, molekuláris genetikai klasszifikáción alapuló modellek célja olyan prognosztikus és prediktív biomarkerek azonosítása, amelyek elősegíthetik a betegek személyre szabott rizikóstratifikációját, valamint potenciális terápiás célpontként szolgálhatnak. Jelen összefoglaló közleményünkben a DLBCL-lel kapcsolatos legfrissebb molekuláris genetikai eredményeket tekintjük át. Summary. Diffuse large B-cell lymphoma is considered to be the most common non-Hodgkin lymphoma, representing 40% of all cases. While almost two third of DLBCL patients can be cured using first line chemoimmunotherapy, the remaining patients develop refractory or relapsed disease with poor outcomes. Despite the wide range of therapeutic options, the success rate in patients poorly responding to chemoimmunotherapy has not met the expectations, potentially resulting from the molecular heterogeneity of the disease. The DLBCL classification used in current diagnostic routine distinguishes three groups based on cell of origin: germinal center B-cell-like, activated B-cell-like and unclassified cases. Even though the GCB subgroup generally has a favorable outcome, compared to the ABC group, there is still a remarkable heterogeneity in each group regarding individual prognosis. Owing to the advances of molecular diagnostic methods, the recently described molecular alterations may serve as cornerstones of a new classification system. Current research focuses on incorporating alterations harboring prognostic or predictive significance into molecular genetic classification systems moving one step closer to paradigm shift in lymphoma management: integrating personalized precision medicine into clinical practice. Hereby, we review the most recent genetic studies, and we provide an overview and comparison of the novel molecular-based DLBCL classification systems published in the past few years.

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