Comprehensive Genomic Studies on the Cell Blocks of Pancreatic Cancer

Autores da FMUP

• 

  Fernando Carlos De Landér Schmitt

  Autor

Participantes de fora da FMUP

• Souza da Silva R.
• Pina M.J.
• Cirnes L.
• Gouveia L.
• Albergaria A.

Unidades de investigação

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Pancreatic cancer is one of the deadliest malignancies, characterized by late-stage diagnosis and limited treatment options. Comprehensive genomic profiling plays an important role in understanding the molecular mechanisms underlying the disease and identifying potential therapeutic targets. Cell blocks (CBs), derived from EUS-FNA, have become valuable resources for diagnosis and genomic analysis. We examine the molecular profile of pancreatic ductal adenocarcinoma (PDAC) using specimens obtained from CB EUS-FNA, across a large gene panel, within the framework of next-generation sequencing (NGS). Our findings revealed that over half (55%) of PDAC CB cases provided adequate nucleic acid for next-generation sequencing, with tumor cell percentages averaging above 30%. Despite challenges such as low DNA quantification and degraded DNA, sequencing reads showed satisfactory quality control statistics, demonstrating the detection of genomic alterations. Most cases (84.6%) harbored at least one gene variant, including clinically significant gene mutation variants such as KRAS, TP53, and CDKN2A. Even at minimal concentrations, as long as the extracted DNA is of high quality, performing comprehensive molecular profiling on PDAC samples from cell blocks has remained feasible. This strategy has yielded valuable information about the diagnosis, genetic landscape, and potential therapeutic targets, aligning closely with a precision cytopathology approach. © 2024 by the authors.

Keywords

• aged; Article; clinical article; controlled study; cytopathology; DNA sequencing; endoscopic ultrasound guided fine needle biopsy; gene mutation; high throughput sequencing; human; human cell; human tissue; minimum concentration; molecular fingerprinting; pancreas cancer; pancreatic ductal carcinoma; quality control