Molecular classification of difficult to diagnose metastatic cancers and characterization of young patients: Clinical experience with the 92-gene assay in >22,000 cases.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11554-11554
Author(s):  
F Anthony Greco ◽  
David R. Spigel ◽  
Theresa N. Operana ◽  
Brock Schroeder ◽  
Junmei Liu ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Young Patients ◽  
Molecular Classification ◽  
Gene Assay

scholarly journals Molecular Classification and Tumor Microenvironment Characterization of Gallbladder Cancer by Comprehensive Genomic and Transcriptomic Analysis

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 733
Author(s):  
Nobutaka Ebata ◽  
Masashi Fujita ◽  
Shota Sasagawa ◽  
Kazuhiro Maejima ◽  
Yuki Okawa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Gallbladder Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Molecular Classification ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Fresh Frozen ◽  
Therapeutic Decision Making

Gallbladder cancer (GBC), a rare but lethal disease, is often diagnosed at advanced stages. So far, molecular characterization of GBC is insufficient, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. We performed a transcriptome analysis of both coding and non-coding RNAs from 36 GBC fresh-frozen samples. The results were integrated with those of comprehensive mutation profiling based on whole-genome or exome sequencing. The clustering analysis of RNA-seq data facilitated the classification of GBCs into two subclasses, characterized by high or low expression levels of TME (tumor microenvironment) genes. A correlation was observed between gene expression and pathological immunostaining. TME-rich tumors showed significantly poor prognosis and higher recurrence rate than TME-poor tumors. TME-rich tumors showed overexpression of genes involved in epithelial-to-mesenchymal transition (EMT) and inflammation or immune suppression, which was validated by immunostaining. One non-coding RNA, miR125B1, exhibited elevated expression in stroma-rich tumors, and miR125B1 knockout in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutation profiles revealed TP53 (47%) as the most commonly mutated gene, followed by ELF3 (13%) and ARID1A (11%). Mutations of ARID1A, ERBB3, and the genes related to the TGF-β signaling pathway were enriched in TME-rich tumors. This comprehensive analysis demonstrated that TME, EMT, and TGF-β pathway alterations are the main drivers of GBC and provides a new classification of GBCs that may be useful for therapeutic decision-making.

Molecular Pathology of Breast Cancer: The Journey From Traditional Practice Toward Embracing the Complexity of a Molecular Classification

2011 ◽  
Vol 135 (5) ◽  
pp. 544-557 ◽  
Author(s):  
Aaron M. Gruver ◽  
Bryce P. Portier ◽  
Raymond R. Tubbs
Keyword(s):  
Molecular Diagnostics ◽  
Treatment Options ◽  
Molecular Classification ◽  
Published Data ◽  
Breast Carcinomas ◽  
Developing Regions ◽  
Traditional Practice ◽  
The Moment

Abstract Context.—Adenocarcinoma of the breast is the most frequent cancer affecting women in both developed and developing regions of the world. From the moment of clinical presentation until the time of pathologic diagnosis, patients affected by this disease will face daunting questions related to prognosis and treatment options. While improvements in targeted therapies have led to increased patient survival, these same advances have created the imperative to accurately stratify patients to achieve maximum therapeutic efficacy while minimizing side effects. In this evolving era of personalized medicine, there is an ever-increasing need to overcome the limitations of traditional diagnostic practice. Objective.—To summarize the molecular diagnostics traditionally used to guide prognostication and treatment of breast carcinomas, to highlight published data on the molecular classification of these tumors, and to showcase molecular assays that will supplement traditional methods of categorizing the disease. Data Sources.—A review of the literature covering the molecular diagnostics of breast carcinomas with a focus on the gene expression and array studies used to characterize the molecular signatures of the disease. Special emphasis is placed on summarizing evolving technologies useful in the diagnosis and characterization of breast carcinoma. Conclusions.—Available and emerging molecular resources will allow pathologists to provide superior diagnostic, prognostic, and predictive information about individual breast carcinomas. These advances should translate into earlier identification and tailored therapy and should ultimately improve outcome for patients affected by this disease.

scholarly journals Molecular and Genetic Analyses of the Putative Proteus O Antigen Gene Locus

2010 ◽  
Vol 76 (16) ◽  
pp. 5471-5478 ◽  
Author(s):  
Quan Wang ◽  
Agnieszka Torzewska ◽  
Xiaojuan Ruan ◽  
Xiaoting Wang ◽  
Antoni Rozalski ◽  
...  
Keyword(s):  
Fragment Length Polymorphism ◽  
Gene Clusters ◽  
Molecular Classification ◽  
Opportunistic Pathogens ◽  
Antigen Gene ◽  
O Antigen ◽  
Tract Infections ◽  
High Degree

ABSTRACT Proteus species are well-characterized opportunistic pathogens primarily associated with urinary tract infections (UTI) of humans. The Proteus O antigen is one of the most variable constituents of the cell surface, and O antigen heterogeneity is used for serological classification of Proteus isolates. Even though most Proteus O antigen structures have been identified, the O antigen locus has not been well characterized. In this study, we identified the putative Proteus O antigen locus and demonstrated this region's high degree of heterogeneity by comparing sequences of 40 Proteus isolates using PCR-restriction fragment length polymorphism (RFLP). This analysis identified five putative Proteus O antigen gene clusters, and the probable functions of these O antigen-related genes were proposed, based on their similarity to genes in the available databases. Finally, Proteus-specific genes from these five serogroups were identified by screening 79 strains belonging to the 68 Proteus O antigen serogroups. To our knowledge, this is the first molecular characterization of the putative Proteus O antigen locus, and we describe a novel molecular classification method for the identification of different Proteus serogroups.

Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 197-197 ◽  
Author(s):  
Michael J. Overman ◽  
Huamin Wang ◽  
Catherine A. Schnabel ◽  
Jeff Anderson ◽  
Mark G. Erlander ◽  
...  
Keyword(s):  
Molecular Classification ◽  
Good Prognosis ◽  
Molecular Profile ◽  
Molecular Testing ◽  
Diagnostic Utility ◽  
Prognostic Performance ◽  
Therapeutic Implications ◽  
Rna Profiling ◽  
Gene Assay

197 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of periampullary adenocarcinomas (PAA) is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 45 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination (pancreatic, extrahepatic biliary, ampullary, or duodenal). Blinded FFPE tumor sections underwent molecular testing and were compared for concordance to histopathological tumor types and prognostic performance. 28 of these samples had previously undergone whole-genome RNA profiling (Overman et al. GI ASCO 2011 a161). Results: Molecular classification of 43 (96%) evaluable samples (13 ampullary, 10 pancreatic, 10 biliary, 10 duodenal) showed 91% concordance: ampullary [5 intestinal (int), 7 pancreaticobiliary (pb)], pancreatic [10 pb], duodenal [3 int, 7 gastroesophageal (ge)], biliary [7 pb]. The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 ampullary and 2 biliary samples, and ovary for 1 biliary case. Previous unsupervised RNA hierarchical clustering of all 13 ampullary cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 cases (5 int and 7 pb). These two ampullary subgroups were prognostic with median OS of 63 vs. 24 m, P=0.07, respectively. Conclusions: The 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA. These results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.

Molecular classification of ampullary adenocarcinoma: Comparative prognostic performance of the 92-gene assay versus histomolecular analysis.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 4141-4141 ◽  
Author(s):  
Aaron Schueneman ◽  
Huamin Wang ◽  
Harris S Soifer ◽  
Catherine A. Schnabel ◽  
Robert A. Wolff ◽  
...  
Keyword(s):  
Molecular Classification ◽  
Ampullary Adenocarcinoma ◽  
Prognostic Performance ◽  
Gene Assay

Immunohistochemical characterization of molecular classification of breast carcinoma and its relation with Ki-67

2016 ◽  
Vol 5 (5) ◽  
pp. 430
Author(s):  
Shabnam Karangadan ◽  
AnuradhaGanesh Patil ◽  
SainathKarnappa Andola
Keyword(s):  
Breast Carcinoma ◽  
Molecular Classification ◽  
Ki 67

Prospective molecular classification of endometrial carcinomas: institutional implementation, practice, and clinical experience

2021 ◽  
Author(s):  
Kelly A. Devereaux ◽  
Julianna J. Weiel ◽  
Jennifer Pors ◽  
David F. Steiner ◽  
Chandler Ho ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Molecular Classification ◽  
Endometrial Carcinomas

scholarly journals Molecular classification of cancer with the 92-gene assay in cytology and limited tissue samples

Oncotarget ◽  
2016 ◽  
Vol 7 (19) ◽  
pp. 27220-27231 ◽  
Author(s):  
Elena F. Brachtel ◽  
Theresa N. Operaña ◽  
Peggy S. Sullivan ◽  
Sarah E. Kerr ◽  
Karen A. Cherkis ◽  
...  
Keyword(s):  
Molecular Classification ◽  
Tissue Samples ◽  
Gene Assay

Diagnostic utility and prognostic performance of a 92-gene cancer classifier to molecularly profile periampullary adenocarcinomas (PAA).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4133-4133
Author(s):  
Michael J. Overman ◽  
Huamin Wang ◽  
Catherine A. Schnabel ◽  
Jeffrey Anderson ◽  
Mark G. Erlander ◽  
...  
Keyword(s):  
Molecular Classification ◽  
Good Prognosis ◽  
Molecular Profile ◽  
Molecular Testing ◽  
Diagnostic Utility ◽  
Prognostic Performance ◽  
Therapeutic Implications ◽  
Gene Assay ◽  
Ffpe Tumor

4133 Background: Due to the small anatomic size, multiplicity of epitheliums, and suboptimal diagnostics determining the site of origin of PAA is a challenge. We investigated the ability of a 92-gene RT-PCR assay (CancerTYPE ID) to categorize PAA and to prognostically stratify ampullary adenocarcinomas. Methods: 171 PAA patients who underwent pancreaticoduodenectomies were included; samples were histopathologically verified for tumor subtype determination: pancreatic (PAN), extrahepatic biliary (EB), ampullary (AMP), or duodenal (DOUD). Blinded FFPE tumor sections underwent molecular testing. Analytical sets were an initial 45 PAA set evaluating concordance to histopathological tumor types and prognostic performance, and a second set of 126 AMP and DOUD adenocarcinoma for validation of prognostic performance. Results: Of the initial 45 patient cohort, molecular classification of 43 (96%) evaluable samples (13 AMP, 10 PAN, 10 EB, 10 DOUD) showed 91% concordance: AMP [5 intestinal (int), 7 pancreaticobiliary (pb)], PAN [10 pb], DOUD [3 int, 7 gastroesophageal (ge)], EB [7 pb]. The 92-gene assay was prognostic with a median OS of 70 m for ge/int cases vs. 32 m for pb cases, P=0.05. Discordant classifications were ge for 1 AMP and 2 EB samples, and ovary for 1 EB case. Previous unsupervised RNA hierarchical clustering (Overman GI ASCO 2011 a161) of all 13 AMP cases had identified two prognostic groups (a good-prognosis int-like and a poor-prognosis pb-like), which were identical to the 92-gene classification for 12 of the 13 cases. Conclusions: In the initial cohort of 45 patients, the 92-gene assay demonstrated diagnostic utility for molecular site-of-origin classification of PAA; evaluation of the remaining 126 ampullary and duodenal cases will be presented. Results support exploration of this approach for the management of metastatic PAA (in which pathologic review of a primary resection specimen is not an option). Molecular classification of ampullary adenocarcinomas into intestinal and pancreaticobiliary subgroups is prognostically relevant; these and the gastric-like molecular profile of duodenal adenocarcinomas may have therapeutic implications.

scholarly journals Molecular Classification of Hepatocellular Adenomas

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jean Charles Nault ◽  
Jessica Zucman Rossi
Keyword(s):  
Young Patients ◽  
Normal Liver ◽  
Molecular Classification ◽  
Basic Knowledge ◽  
Benign Tumors ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocellular Adenomas ◽  
Diagnostic Pitfalls

Hepatocellular adenomas (HCAs) are benign tumors developed in normal liver most frequently in women before menopause. HCAs lead to diagnostic pitfalls and several difficulties to assess the risk of malignant transformation in these young patients. Recent advances in basic knowledge have revealed a molecular classification related to risk factors, pathological features, and risk of transformation in hepatocellular carcinoma. Three major molecular pathways have been identified altered in specific HCA subgroups that are defined by either (1) inactivation of hepatocyte nuclear factor 1A (HNF1A) transcription factor, (2) activation of the WNT/β-catenin byCTNNB1mutations, or (3) activation of the IL6/STAT3 pathway by somatic mutation ofIL6ST,GNAS, orSTAT3. Here, we will review the different molecular classes of HCA.

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