Evaluating Pancreatic and Biliary Neoplasms with Small Biopsy-Based Next Generation Sequencing (NGS): Doing More with Less

Pancreatic cancer and cholangiocarcinoma are lethal diseases mainly diagnosed at an inoperable stage. As pancreatobiliary surgical specimens are often unavailable for further molecular testing, this review aimed to highlight the diagnostic, prognostic, and therapeutic impact of next-generation sequencing (NGS) performed on distinct small biopsies, including endoscopic ultrasound fine-needle aspirations and biopsies of pancreatic solid and cystic lesions, biliary duct brushings, and also “liquid biopsies” such as the pancreatic juice, bile, and blood. NGS could clarify indeterminate pancreatic lesions or biliary strictures, for instance by identifying TP53 or SMAD4 mutations indicating high-grade dysplasia or cancer. It could also stratify pancreatic cystic lesions, by distinguishing mucinous from non-mucinous cysts and identifying high-risk cysts that should be excised in surgically fit patients, whereas the combination of cytology, elevated cystic CEA levels and NGS could improve the overall diagnostic accuracy. When NGS is performed on the pancreatic juice, it could stratify high-risk patients under surveillance. On the plasma, it could dynamically monitor the disease course and response to therapy. Notably, the circulating tumor DNA (ctDNA) levels have been associated with staging, grading, and survival. Lastly, NGS has shown potential in identifying potentially actionable molecular alterations. In conclusion, NGS applied on small biopsies could carry significant diagnostic, prognostic, and therapeutic value.

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Next-generation sequencing (NGS) in metastatic colorectal cancer (mCRC): Novel mutated genes and their effect on response to therapy (Alliance)

Annals of Oncology ◽

10.1093/annonc/mdz246.002 ◽

2019 ◽

Vol 30 ◽

pp. v198-v199

Author(s):

F. Innocenti ◽

N. Rashid ◽

M. Wancen ◽

F.-S. Ou ◽

X. Qu ◽

...

Keyword(s):

Colorectal Cancer ◽

Next Generation Sequencing ◽

Metastatic Colorectal Cancer ◽

Response To Therapy ◽

Next Generation ◽

Therapy Alliance ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

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Synchronous Pulmonary Adenocarcinomas

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa023 ◽

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).

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Characterization and Diversity of 243 Complete Human Papillomavirus Genomes in Cervical Swabs Using Next Generation Sequencing

Viruses ◽

10.3390/v12121437 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1437

Author(s):

Ardashel Latsuzbaia ◽

Anke Wienecke-Baldacchino ◽

Jessica Tapp ◽

Marc Arbyn ◽

Irma Karabegović ◽

...

Keyword(s):

Human Papillomavirus ◽

Next Generation Sequencing ◽

High Risk ◽

Pairwise Distance ◽

Next Generation ◽

Hpv Genotypes ◽

Complete Genomes ◽

Hpv Types ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

In recent years, next generation sequencing (NGS) technology has been widely used for the discovery of novel human papillomavirus (HPV) genotypes, variant characterization and genotyping. Here, we compared the analytical performance of NGS with a commercial PCR-based assay (Anyplex II HPV28) in cervical samples of 744 women. Overall, HPV positivity was 50.2% by the Anyplex and 45.5% by the NGS. With the NGS, we detected 25 genotypes covered by Anyplex and 41 additional genotypes. Agreement between the two methods for HPV positivity was 80.8% (kappa = 0.616) and 84.8% (kappa = 0.652) for 28 HPV genotypes and 14 high-risk genotypes, respectively. We recovered and characterized 243 complete HPV genomes from 153 samples spanning 40 different genotypes. According to phylogenetic analysis and pairwise distance, we identified novel lineages and sublineages of four high-risk and 16 low-risk genotypes. In total, 17 novel lineages and 14 novel sublineages were proposed, including novel lineages of HPV45, HPV52, HPV66 and a novel sublineage of HPV59. Our study provides important genomic insights on HPV types and lineages, where few complete genomes were publicly available.

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Next-Generation Sequencing Informing Therapeutic Decisions and Personalized Approaches

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_159017 ◽

2016 ◽

pp. e442-e448 ◽

Cited By ~ 3

Author(s):

Raphael Szalat ◽

Nikhil C. Munshi

Keyword(s):

Next Generation Sequencing ◽

High Risk ◽

Proteasome Inhibitors ◽

Next Generation ◽

Current State ◽

Therapeutic Decisions ◽

High Risk Disease ◽

Risk Patients ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Multiple myeloma is a heterogeneous disease featured by different molecular subtypes. In the last decade, new therapeutics including second- and third-generation proteasome inhibitors and immunomodulatory agents, monoclonal antibodies, and other novel targeted agents have completely transformed the outcome of the disease. The task ahead is to develop strategies to identify effective combinations and sequences of agents that can exploit the genetic make-up of myeloma cells to improve efficacy. Moreover, a subgroup of high-risk patients who experience early disease relapse and shorter survival also requires early identification and specific intervention. Next-generation sequencing (NGS) technologies now allow us to accomplish some of these goals. As described here, besides improving our understanding of the disease, it is beginning to influence our clinical decisions and therapeutic choices. In this article, we describe the current state-of-the-art role of NGS in myeloma from identifying high-risk disease, to drug selection, and, ultimately, to guide personalized therapy.

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