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Methods in Molecular Biology (Clifton,... 2022Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies...
Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies depends on a number of factors such as mutational burden, neoantigen load, presence of tumor infiltrating lymphocytes, among others. Next-generation sequencing (NGS) technologies are particularly attractive to interrogate the immune response compared to traditional assays such as qRT-PCR and immunohistochemistry (IHC) because they enable the discovery of neoantigens and simultaneous profiling of immune infiltration using gene expression on a large scale. Current approaches in immune profiling utilizes whole-exome sequencing (WES) for human leukocyte allele (HLA) typing and neoantigen predictions, and RNA sequencing (RNA-seq) for filtering unexpressed neoantigens and inferring immune infiltration. They have been successfully applied to the tumor setting as there is abundant sample material to perform both experiments. However, premalignant specimens are often much smaller compared to tumors. Therefore, there is a need to explore the viability of adopting a single approach for immune, neoantigen, and mutation profiling. Here, we describe our workflow of using RNA-seq to analyze mutational burden, neoantigen load, and immune expression profile.
Topics: Antigens, Neoplasm; Humans; Lymphocytes, Tumor-Infiltrating; Mutation; Precancerous Conditions; Transcriptome; Exome Sequencing
PubMed: 34993941
DOI: 10.1007/978-1-0716-2014-4_7 -
The American Journal of Pathology Jan 2019Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms with poor outcomes. At the time of diagnosis, the disease is usually at an advanced... (Review)
Review
Pancreatic ductal adenocarcinoma is one of the most aggressive malignant neoplasms with poor outcomes. At the time of diagnosis, the disease is usually at an advanced stage and only a minority is eligible for surgical resection. To improve the prognosis, it is essential to diagnose and treat the disease in an early stage before its progression into an invasive disease. This article reviews clinical features, histopathology, cytopathology, and molecular alterations of pancreatic ductal adenocarcinoma and its precursors. Moreover, we review a recently updated two-tier classification system for precursor lesions, new findings in premalignant cystic neoplasms, and recently updated staging criteria for invasive carcinoma based on the Cancer Staging Manual, eighth edition, from the American Joint Committee on Cancer. Finally, we discuss the potential clinical applications of the rapidly growing molecular and genetic information of pancreatic cancer and its precursors.
Topics: Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Humans; Neoplasm Staging; Pancreatic Neoplasms; Precancerous Conditions
PubMed: 30558727
DOI: 10.1016/j.ajpath.2018.10.004 -
Biochemistry. Biokhimiia May 2008In this essay crucial problems of the origin of cancer and the development of malignancy are discussed. The problem of precancer and three ways leading to malignancy are... (Review)
Review
In this essay crucial problems of the origin of cancer and the development of malignancy are discussed. The problem of precancer and three ways leading to malignancy are considered: induction of tumor precursors, accumulation of genetic traits common for tumor growth, and the role of inflammation in tumor induction. The nature of viral oncogenes and modes of their action are described in the context of their origin as a component of the viral genome. Oncogenes of RNA-containing viruses and DNA-containing tumorigenic viruses are described together with cellular protooncogenes, which are progenitors of RNA-containing viral oncogenes. Hematological malignancies are described as an intermediate form between simple tumors induced by a single oncogene and more complicated epithelial tumors. The roles of tumor suppressor genes and the interaction of several oncogenes in the formation of carcinomas and also the role of progression in tumor evolution are discussed.
Topics: Animals; Carcinoma; Genes, Tumor Suppressor; Humans; Neoplasms; Oncogenes; Precancerous Conditions; Proto-Oncogenes
PubMed: 18605973
DOI: 10.1134/s0006297908050015 -
Annals of Medicine Dec 2023The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma.
OBJECTIVE
The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma.
METHODS
We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications.
RESULTS
A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type ( = 0.009) and Lugano classification stage IIE + IV ( < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma ( < 0.001), Lugano classification stage I + II ( < 0.001), and patients complicated with precancerous conditions and gastric cancer ( < 0.001), especially gastric cancer of the intestinal type ( = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.
CONCLUSIONS
Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer.Key messages5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer.14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%).Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.
Topics: Humans; Lymphoma, B-Cell, Marginal Zone; Stomach Neoplasms; Retrospective Studies; Helicobacter Infections; Helicobacter pylori; Atrophy; Adenocarcinoma; Precancerous Conditions; Metaplasia
PubMed: 37183786
DOI: 10.1080/07853890.2023.2193423 -
Seminars in Oncology Feb 2016The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was... (Review)
Review
The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures.
Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Epigenesis, Genetic; Genetic Predisposition to Disease; Genomics; Humans; Neoplasms; Neoplastic Stem Cells; Precancerous Conditions; Risk Assessment
PubMed: 26970122
DOI: 10.1053/j.seminoncol.2015.09.007 -
Experimental Hematology Mar 2020Over the course of the human life span, somatic DNA mutations accumulate in healthy tissues. This process has been most clearly described in blood and bone marrow,... (Review)
Review
Over the course of the human life span, somatic DNA mutations accumulate in healthy tissues. This process has been most clearly described in blood and bone marrow, esophagus, colon, and skin, but cumulative DNA damage likely affects all tissues of the body. Although most acquired genetic variants have no discernable functional consequences, some randomly occurring somatic mutations confer a relative fitness advantage on a single stem cell and its progeny compared with surrounding cells, which may lead to progressive expansion of a clone (i.e., a genetically identical group of cells). When these mutations occur in a cell with the capacity to self-renew and expand, the mutations persist, and such clonal expansion is a risk factor for further mutation acquisition and clonal evolution. Hematopoietic stem cells are a special case of clonal expansion because both the stem cells and their blood cell progeny circulate in large numbers, and these cells are not subject to some of the anatomical restrictions that characterize other tissues in which somatic mutations conferring a fitness advantage also occur. Therefore, clonally restricted hematopoiesis can have biological and clinical consequences that are distinct from clonal expansions in other tissues. Such consequences include not only clonal progression to overt myeloid neoplasia (or, less commonly, to lymphoid neoplasia) driven by acquisition of secondary mutations in the cells of the expanded clone, but also cardiovascular events and, most likely, other diseases that are influenced by aberrant function of mutant blood cells. A more detailed understanding of how clonal hematopoiesis arises and how clonal selection and expansion occur, as well as development of strategies to avert the clinical consequences associated with clonal hematopoiesis, may both improve public health and yield more general insights into the biology of aging.
Topics: Aging; Alleles; Hematologic Neoplasms; Hematopoiesis; Humans; Mutation; Precancerous Conditions; Risk Factors
PubMed: 31838005
DOI: 10.1016/j.exphem.2019.12.001 -
Disease Markers 2018Hu-antigen R (HuR) is a posttranscriptional regulator of several target mRNAs, implicated in carcinogenesis. This review aims to present the current evidence regarding... (Review)
Review
BACKGROUND
Hu-antigen R (HuR) is a posttranscriptional regulator of several target mRNAs, implicated in carcinogenesis. This review aims to present the current evidence regarding the biological role and potential clinical significance of HuR in head and neck carcinomas.
METHODS
The existing literature concerning HuR expression and function in head and neck carcinomas is critically presented and summarised.
RESULTS
HuR is expressed in the majority of the examined samples, showing higher cytoplasmic levels in malignant or premalignant cases. Moreover, HuR modulates several genes implicated in biological processes important for malignant transformation, growth, and invasiveness. HuR seems to be an adverse prognosticator in patients with OSCCs, whereas a correlation with a more aggressive phenotype is reported in several types of carcinomas.
CONCLUSIONS
A consistent role of HuR in the carcinogenesis and progression of head and neck carcinomas is suggested; nevertheless, further studies are warranted to expand the present information.
Topics: Biomarkers, Tumor; Cytoplasm; ELAV-Like Protein 1; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Head and Neck Neoplasms; Humans; Precancerous Conditions; Prognosis; Up-Regulation
PubMed: 29619127
DOI: 10.1155/2018/4020937 -
World Journal of Gastroenterology Jul 2016Barrett's esophagus (BE) is an important condition given its significant premalignant potential and dismal five-year survival outcomes of advanced esophageal... (Review)
Review
Barrett's esophagus (BE) is an important condition given its significant premalignant potential and dismal five-year survival outcomes of advanced esophageal adenocarcinoma. It is therefore suggested that patients with a diagnosis of BE undergo regular surveillance in order to pick up dysplasia at an earlier stage to improve survival. Current "gold-standard" surveillance protocols suggest targeted biopsy of visible lesions followed by four quadrant random biopsies every 2 cm. However, this method of Barrett's surveillance is fraught with poor endoscopist compliance as the procedures are time consuming and poorly tolerated by patients. There are also significant miss-rates with this technique for the detection of neoplasia as only 13% of early neoplastic lesions appear as visible nodules. Despite improvements in endoscope resolution these problems persist. Chromoendoscopy is an extremely useful adjunct to enhance mucosal visualization and characterization of Barrett's mucosa. Acetic acid chromoendoscopy (AAC) is a simple, non-proprietary technique that can significantly improve neoplasia detection rates. This topic highlight summarizes the current evidence base behind AAC for the detection of neoplasia in BE and provides an insight into the direction of travel for further research in this area.
Topics: Acetic Acid; Adenocarcinoma; Barrett Esophagus; Esophageal Neoplasms; Esophagoscopy; Humans; Indicators and Reagents; Precancerous Conditions
PubMed: 27433088
DOI: 10.3748/wjg.v22.i25.5753 -
Australian Dental Journal Sep 2011Despite recent advances in therapy and treatment for oral cancer, survival rates are still low. It is generally accepted that oral cancer may arise from potentially... (Review)
Review
Despite recent advances in therapy and treatment for oral cancer, survival rates are still low. It is generally accepted that oral cancer may arise from potentially premalignant disorders. Oral erythroplakia has been identified as the one with the highest malignant transformation rates. The aim of this review was to provide detailed information on oral cancer and oral erythroplakia. Few data are available on oral erythroplakia and there is an urgent need for randomized controlled trials. Early detection and diagnosis is still the key to survival rates. Dentists and physicians may play an important role in the detection of premalignant lesions and therefore improve patients' outcome.
Topics: Cell Transformation, Neoplastic; Diagnosis, Differential; Disease Progression; Early Detection of Cancer; Erythroplasia; Humans; Mouth Neoplasms; Precancerous Conditions; Survival Rate
PubMed: 21884139
DOI: 10.1111/j.1834-7819.2011.01337.x -
Oral Surgery, Oral Medicine, Oral... Jun 2018Potentially malignant oral mucosal disease has some ability to give rise to malignancy of the oral epithelium, that is, oral squamous cell carcinoma (OSCC). The present... (Review)
Review
Potentially malignant oral mucosal disease has some ability to give rise to malignancy of the oral epithelium, that is, oral squamous cell carcinoma (OSCC). The present article provides a succinct review of the possible or probable causes of potentially premalignant oral epithelial lesions. There is a focus upon studies that examined the causes or etiologic associations with clinically likely or histopathologically detectable oral epithelial dysplasia.
Topics: Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Diagnosis, Oral; Disease Progression; Erythroplasia; Humans; Leukoplakia, Oral; Mouth Neoplasms; Precancerous Conditions; Risk Factors
PubMed: 29891084
DOI: 10.1016/j.oooo.2018.03.008