2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Evaluation of PMS2 gene variant c.2182_2184delinsG by NGS in a Brazilian sample. How Long-Range PCR can solve homology?

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This study focuses on the evaluation of a specific gene variant (c.2182_2184delinsG) in the PMS2 gene in a Brazilian sample. The PMS2 gene is associated with Lynch syndrome, which is the leading cause of hereditary colorectal cancer. However, molecular testing of this gene is challenging due to its high homology with the PMS2CL pseudogene. Next-generation sequencing (NGS) can detect the presence of a variant but cannot differentiate whether it is in the gene or pseudogene. Therefore, the researchers employed Long-Range PCR as a solution to address this issue. <br /><br />The study selected 39 samples with the variant identified by NGS and performed Long-Range PCR amplifications of the specific segment in question. This approach could differentiate whether the variant was located in the gene or the pseudogene. The amplified samples were then purified and subjected to Sanger sequencing to confirm the results. <br /><br />The findings showed that the variant c.2182_2184delinsG detected by NGS was not confirmed by Long-Range PCR, indicating its absence in the PMS2 gene. The study could not establish a correlation between the molecular findings and tumor MMR status or microsatellite instability analysis due to a lack of access to this data. <br /><br />In conclusion, the use of Long-Range PCR was found to be a reliable approach for accurately analyzing PMS2 gene variants in segments with high homology with the PMS2CL pseudogene. Confirming such variants is crucial to avoid misdiagnosis of Lynch syndrome and ensure appropriate genetic counseling and clinical management for patients and their families.

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Co-Author - Daniele Paixão, MD, MSc, PhD; Co-Author - Thalitta Hetamaro Ayala Lima, PhD; Presenting Author - Larissa Souza Mario Bueno, MD; Co-Author - Rafaela Rogério Floriano de Souza, MSc; Co-Author - Juliana Emilia Prior Carnavalli, MSc; Co-Author - Clarissa Gondim Picanço-Albuquerque, PhD; Co-Author - Isabelle Joyce de Lima Silva-Fernandes, PhD; Co-Author - Paulo Goberlânio de Barros Silva, PhD; Co-Author - Miguel Mitne-Neto, PhD; Co-Author - Wagner Antônio da Rosa Baratela, MD, PhD; Co-Author - Caroline Mônaco Moreira, MSc;

Meta Tag

Cancer Syndromes

Genetic Testing

Genomic Methodologies

NextGen Sequencing

Co-Author Daniele Paixão, MD, MSc, PhD

Co-Author Thalitta Hetamaro Ayala Lima, PhD

Co-Author Rafaela Rogério Floriano de Souza, MSc

Co-Author Juliana Emilia Prior Carnavalli, MSc

Co-Author Clarissa Gondim Picanço-Albuquerque, PhD

Co-Author Isabelle Joyce de Lima Silva-Fernandes, PhD

Co-Author Paulo Goberlânio de Barros Silva, PhD

Co-Author Miguel Mitne-Neto, PhD

Co-Author Wagner Antônio da Rosa Baratela, MD, PhD

Co-Author Caroline Mônaco Moreira, MSc

Presenting Author Larissa Souza Mario Bueno, MD

Keywords

gene variant

PMS2 gene

Brazilian sample

Lynch syndrome

hereditary colorectal cancer

molecular testing

homology

PMS2CL pseudogene

Next-generation sequencing

Long-Range PCR