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Genetics in Medicine : Official Journal... Dec 2018
Topics: Adenosine Monophosphate; Consensus; Genetics, Medical; Genomics; Pathology, Molecular; United States
PubMed: 29543229
DOI: 10.1038/gim.2018.42 -
American Journal of Transplantation :... Apr 2022
Topics: Allografts; Bronchiolitis Obliterans; Graft Rejection; Humans; Lung; Lung Transplantation; Pathology, Molecular
PubMed: 34910363
DOI: 10.1111/ajt.16925 -
Surgical Pathology Clinics Sep 2021Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and... (Review)
Review
Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.
Topics: Carcinoma, Transitional Cell; Genomics; Humans; Pathology, Molecular; Urinary Bladder Neoplasms
PubMed: 34373092
DOI: 10.1016/j.path.2021.05.005 -
Advances in Oto-rhino-laryngology 2016The field of salivary gland tumor biology is quite broad, given the numerous subtypes of both benign and malignant tumors originating from the major and minor salivary... (Review)
Review
The field of salivary gland tumor biology is quite broad, given the numerous subtypes of both benign and malignant tumors originating from the major and minor salivary glands. Knowledge about the molecular pathology of these lesions is still limited, and there are few clinically useful diagnostic and prognostic biomarkers. However, recent discoveries of certain key genomic alterations, such as chromosome translocations, copy number alterations, and mutations, provide new insights into the molecular pathogenesis of these lesions and may help to better define them. It is also hoped that this new knowledge can help to guide therapy, but this translation has been somewhat slow to develop, perhaps due to the rarity of these tumors and the lack of large, randomized studies. However, because of the limitations inherent in what surgery and radiation can provide, there is an urgent need for understanding of the mechanisms of carcinogenesis in these tumors individually, so that chemotherapy and/or targeted therapy can be rationally selected.
Topics: Biomarkers, Tumor; Humans; Pathology, Molecular; Salivary Gland Neoplasms
PubMed: 27092959
DOI: 10.1159/000442121 -
Archives of Pathology & Laboratory... Oct 2022The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or...
Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer.
CONTEXT.—
The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status.
OBJECTIVE.—
To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy.
DESIGN.—
The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope.
RESULTS.—
Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract.
CONCLUSIONS.—
An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories.
Topics: Female; Humans; Colorectal Neoplasms; DNA Mismatch Repair; Immune Checkpoint Inhibitors; Microsatellite Instability; Pathologists; Pathology, Molecular; Systematic Reviews as Topic
PubMed: 35920830
DOI: 10.5858/arpa.2021-0632-CP -
International Journal of Molecular... Jul 2022Today, the oncologist is like a detective of the human body who, instead of a magnifying glass, uses the new tools of molecular pathology to search not only for genes or...
Today, the oncologist is like a detective of the human body who, instead of a magnifying glass, uses the new tools of molecular pathology to search not only for genes or molecular targets, to be targeted with innovative anticancer therapies, but also molecular alterations that allow the identification of population groups at risk of developing tumors for preventive purposes [...].
Topics: Humans; Molecular Targeted Therapy; Neoplasms; Pathology, Molecular; Therapies, Investigational
PubMed: 35955561
DOI: 10.3390/ijms23158429 -
The Journal of Molecular Diagnostics :... Mar 2019Although classic histomorphology is the cornerstone of bone tumor diagnostics, this field has rapidly evolved since the advancement of new molecular techniques. The... (Review)
Review
Although classic histomorphology is the cornerstone of bone tumor diagnostics, this field has rapidly evolved since the advancement of new molecular techniques. The identification of novel genetic alterations in bone tumors has led to more insight into the genetic background of these tumors, which has resulted in a more prominent role of molecular pathology in daily practice. Numerous studies have been conducted in the past few decades and illustrated that based on molecular alterations, bone tumors can be roughly classified as tumors with simple karyotypes and those with complex karyotypes. The first group can be subclassified as tumors that carry specific translocations, somatic gene mutations, or more or less specific amplifications. On the other hand, sarcomas with complex karyotypes usually lack specific alterations. Many techniques are available for the detection of recurrent genetic alterations, now also including IHC analysis, and this review focuses on assays routinely performed in molecular diagnostics. Subsequently, tumor classes with distinct genetic abnormalities are discussed and illustrated by more specific examples, and the usefulness of molecular pathology in routine diagnostics is highlighted.
Topics: Animals; Bone Neoplasms; Humans; Karyotyping; Mutation; Pathology, Molecular; Sarcoma; Translocation, Genetic
PubMed: 30572118
DOI: 10.1016/j.jmoldx.2018.11.002 -
Cells Sep 2022Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis due to the lack of methods or biomarkers for early diagnosis and its resistance to conventional... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis due to the lack of methods or biomarkers for early diagnosis and its resistance to conventional treatment modalities, targeted therapies, and immunotherapies. PDACs are a heterogenous group of malignant epithelial neoplasms with various histomorphological patterns and complex, heterogenous genetic/molecular landscapes. The newly proposed molecular classifications of PDAC based on extensive genomic, transcriptomic, proteomic and epigenetic data have provided significant insights into the molecular heterogeneity and aggressive biology of this deadly disease. Recent studies characterizing the tumor microenvironment (TME) have shed light on the dynamic interplays between the tumor cells and the immunosuppressive TME of PDAC, which is essential to disease progression, as well as its resistance to chemotherapy, newly developed targeted therapy and immunotherapy. There is a critical need for the development of predictive markers that can be clinically utilized to select effective personalized therapies for PDAC patients. In this review, we provide an overview of the histological and molecular heterogeneity and subtypes of PDAC, as well as its precursor lesions, immunosuppressive TME, and currently available predictive molecular markers for patients.
Topics: Biomarkers; Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms; Pathology, Molecular; Proteomics; Tumor Microenvironment
PubMed: 36231030
DOI: 10.3390/cells11193068 -
Annual Review of Genomics and Human... Aug 2022Molecular diagnostic tests enable rapid analysis of genomic and proteomic markers. These tests are subject to diverging premarket access and postmarket surveillance... (Review)
Review
Molecular diagnostic tests enable rapid analysis of genomic and proteomic markers. These tests are subject to diverging premarket access and postmarket surveillance requirements and mechanisms in the United States and the European Union. Each of these jurisdictions has its own challenges in keeping the regulations up to date with technological developments. A specific area of attention is that of laboratory-developed tests in the United States and health institution in-house-produced tests in the European Union, for which the United States and the European Union have markedly different regulatory approaches. Both jurisdictions have specific but differing requirements for the use of test samples and test-related data under their rules regarding the protection of (personal) health data, which can cause complexity when moving samples or sample-related data from one jurisdiction to the other.
Topics: European Union; Humans; Pathology, Molecular; Proteomics; United States; United States Food and Drug Administration
PubMed: 36044907
DOI: 10.1146/annurev-genom-121521-010416 -
Surgical Pathology Clinics Sep 2021Breast cancer is a heterogenous disease with various histologic subtypes, molecular profiles, behaviors, and response to therapy. After the histologic assessment and... (Review)
Review
Breast cancer is a heterogenous disease with various histologic subtypes, molecular profiles, behaviors, and response to therapy. After the histologic assessment and diagnosis of an invasive breast carcinoma, the use of biomarkers, multigene expression assays and mutation profiling may be used. With improved molecular assays, the identification of somatic genetic alterations in key oncogenes and tumor suppressor genes are playing an increasingly important role in many areas of breast cancer care. This review summarizes the most clinically significant somatic alterations in breast tumors and how this information is used to facilitate diagnosis, provide potential treatment options, and identify mechanisms of resistance.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Mutation; Oncogenes; Pathology, Molecular
PubMed: 34373096
DOI: 10.1016/j.path.2021.05.009