scholarly journals What’s new in molecular genetic pathology 2021: solid tumors and NGS panel selection

2021 ◽  
Vol 55 (6) ◽  
pp. 421-422
Author(s):  
Guoli Chen ◽  
Patricia C. Tsang
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Digestive System ◽  
Molecular Genetic ◽  
Genomic Testing ◽  
Molecular Testing ◽  
Next Generation Sequencing Ngs ◽  
To Receive ◽  
Generation Sequencing ◽  
Therapeutic Responses

The linchpin of precision medicine is molecular genetic and genomic testing. Molecular biomarkers are important for establishing precise diagnoses and for predicting therapeutic responses that enable cancer patients to receive personalized and targeted treatment. Below are highlights of the current considerations in next generation sequencing (NGS) panel selection, and in molecular testing of solid tumors of the lung, digestive system, thyroid and soft tissue.

PLAG1 Immunohistochemical Staining Is a Surrogate Marker for PLAG1 Fusions in Lipoblastomas

2021 ◽  
pp. 109352662110433
Author(s):  
Mikako Warren ◽  
Nishant Tiwari ◽  
Sabrina Sy ◽  
Gordana Raca ◽  
Ryan J Schmidt ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gold Standard ◽  
Immunohistochemical Staining ◽  
Surrogate Marker ◽  
Molecular Testing ◽  
Protein Overexpression ◽  
Conventional Cytogenetics ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Lipomatous Tumors

Background The hallmark of lipoblastoma is a PLAG1 fusion. PLAG1 protein overexpression has been reported in sporadic PLAG1-rearranged lipoblastomas. Methods We evaluated the utility of PLAG1 immunohistochemical staining (IHC) in 34 pediatric lipomatous tumors, correlating the results with histology and conventional cytogenetics, FISH and/or next generation sequencing (NGS) results. Results The study included 24 lipoblastomas, divided into 2 groups designated as “Lipoblastoma 1” with both lipoblastoma histology and PLAG1 rearrangement (n = 16) and “Lipoblastoma 2” with lipoblastoma histology but without PLAG1 cytogenetic rearrangement (n = 8), and 10 lipomas with neither lipoblastoma histology nor a PLAG1 rearrangement. Using the presence of a fusion as the “gold standard” for diagnosing lipoblastoma (Lipoblastoma 1), the sensitivity of PLAG1 IHC was 94%. Using histologic features alone (Lipoblastoma 1 + 2), the sensitivity was 96%. Specificity, as defined by the ability to distinguish lipoma from lipoblastoma, was 100%, as there were no false positives in the lipoma group. Conclusions Cytogenetics/molecular testing is expensive and may not be ideal for detecting PLAG1 fusions because PLAG1 fusions are often cytogenetically cryptic and NGS panels may not include all partner genes. PLAG1 IHC is an inexpensive surrogate marker of PLAG1 fusions and may be useful in distinguishing lipoblastomas from lipomas.

scholarly journals Synchronous Pulmonary Adenocarcinomas

2020 ◽  
Vol 154 (1) ◽  
pp. 57-69
Author(s):  
Carlos A Pagan ◽  
Catherine A Shu ◽  
John P Crapanzano ◽  
Galina G Lagos ◽  
Mark B Stoopler ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gene Panel ◽  
Driver Mutations ◽  
Molecular Testing ◽  
Next Generation ◽  
Synchronous Tumors ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Objectives To determine concordance/discordance between morphology and molecular testing (MT) among synchronous pulmonary carcinomas using targeted next generation sequencing (NGS), with and without comprehensive molecular review (CMR), vs analyses of multiple singe genes (non-NGS). Methods Results of morphologic and MT assessment were classified as concordant, discordant, or indeterminate. For discordant cases, comprehensive histologic assessment (CHA) was performed. Results Forty-seven cases with 108 synchronous tumors were identified and underwent MT (NGS, n = 23 and non-NGS, n = 24). Histology and MT were concordant, discordant, and indeterminate in 53% (25/47), 21% (10/47), and 26% (12/47) of cases, respectively. CHA of the 10 discordant cases revised results of three cases. Conclusions There is discordance between histology and MT in a subset of cases and MT provides an objective surrogate for staging synchronous tumors. A limited gene panel is sufficient for objectively assessing a relationship if the driver mutations are distinct. Relatedness of mutations require CMR with a larger NGS panel (eg, 50 genes).

Mutational landscape of AKT1/2/3 in Chinese patients with solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Hui Kong ◽  
Weijia Fang ◽  
Haibo Mou ◽  
Feng Xiao Chen ◽  
Lingxiang Liu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Chinese Patients ◽  
Great Promise ◽  
Central Component ◽  
Next Generation ◽  
Gene Panel Testing ◽  
Different Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

e15566 Background: As a central component of PI3K/AKT pathway, AKT serves as an attractive target of anti-cancer strategy with various AKT inhibitors, which show great promise in phase I/II clinical trials. This study aimed to investigate AKT1/2/3 status in different types of cancers by using next generation sequencing (NGS). Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10,010 Chinese patients with solid tumors and subjected to next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations, tumor mutational burden (TMB) values, and microsatellite instability (MSI) status were assessed with a mean coverage of 1000X, including single base substitutions, short and long insertion/deletions, copy number variations, gene fusions, and rearrangements. Genomic data and immune checkpoint inhibitors (ICIs) treatment outcome of a cohort of 1610 patients with solid tumors were derived from cBioPortal (MSKCC, Nat Genet. 2019). Results: AKT1/2/3 were found to be mutually exclusive with each other and accounted for 3.4% in this cohort. The frequencies of AKT1/2/3 variations were 1.1%, 1.6%, and 0.8%, respectively. The most common co-altered genes associated with AKT1/2/3 variations were TP53 (69.4%), PIK3CA (19.3%), KRAS (19%), CCNE1 (18.4%), CDKN2A (16.6%), and 11q13 (6.5%). AKT1/2/3 variations were significantly associated with higher TMB, and independent of MSI status. Outcome data from the MSKCC cohort showed that patients with AKT1/2/3 variations had a remarkable clinical benefit to ICIs treatment compared to patients with wild-type AKT1/2/3 in overall survival (OS) (NA vs 18 months, p = 0.009). Furthermore, AKT1/2/3 variations were independent risk factors of OS (HR: 0.55, 95%CI: 0.34-0.87, p = 0.012). Conclusions: The prevalence of AKT1/2/3 somatic alterations across different types of solid tumors in China was 3.4%. AKT1/2/3 variations were associated with an increased TMB and favorable response to ICIs, suggesting that A KT1/2/3 variations may be biomarkers for guiding anti-AKT agents and ICI treatment.

Classification of somatic variants in solid tumors detected by next-generation sequencing (NGS) and the need for clinical guidelines.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1555-1555
Author(s):  
Antonios Papanicolau-Sengos ◽  
Edward Hart ◽  
Wei Shen ◽  
Kenneth F. Grossmann ◽  
Cecily Vaughn ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Clinical Guidelines ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

ERBB2 mutation profiling with next-generation sequencing (NGS) in solid tumors.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24264-e24264
Author(s):  
Fei Ma ◽  
Min Zhang ◽  
Quchang Ouyang ◽  
Jun Zhao ◽  
Xiaorong Dong ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Mutation Profiling
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