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PPGCS PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE PRÓ-REITORIA DE PESQUISA E PÓS-GRADUAÇÃO Phone: Not available E-mail: melinapinheiro@ufsj.edu.br http://www.ufsj.edu.br//ppgcs

Banca de QUALIFICAÇÃO: MARCUS VINÍCIUS GONÇALVES ANTUNES

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MARCUS VINÍCIUS GONÇALVES ANTUNES
DATE: 06/12/2023
TIME: 09:00
LOCAL: Videoconferência
TITLE:

Bioinformatics in the investigation of the molecular bases of Hereditary Syndrome Breast and Ovarian Cancer in Minas Gerais

KEY WORDS:

HBOC, NCCN, Genetic counseling, Bioinformatics.

PAGES: 153
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Cancer has become one of the leading global causes of death. In Brazil

alone, for the triennium from 2023 to 2025, the National Cancer Institute (INCA)

estimates that around 704 thousand cases will be registered. Female breast cancer

is the second most incident, with 74 thousand records, and is the most common in all

regions of the country. In contrast, ovarian cancer ranks eighth, with an estimated

7.3 thousand cases for the same triennium. Among the risk factors, genetic factors

play a crucial role, with 10 to 15% of ovarian cancer cases and 5 to 10% of breast

cancer cases related to germline mutations, characterizing hereditary breast and

ovarian cancer syndrome (HBOC). Mutations in various genes may be associated

with this syndrome. In this context, the use of advanced technologies, such as

next-generation sequencing (NGS) and multigene panels, has been crucial for

precision medicine in the diagnosis and monitoring of cancer patients. This study

aims to optimize bioinformatics tools for mutation identification in patients from the

Center-West of Minas Gerais served by the SUS who meet clinical criteria for HBOC.

Regions of exons, 3' and 5' UTR portions, and splicing sites of 22 genes from 72

probands were sequenced, following the guidelines of the National Comprehensive

Cancer Network (NCCN). Bioinformatics analyses were conducted by two distinct

pipelines: the DNA Amplicom application from Illumina and the independent pipeline

developed by the Laboratory of Human Genetic Diversity (LDGH) at UFMG, adapted

for this study. The FASTQ files generated in the sequencing showed high quality,

with over 19 million reads, of which 96% had a Phred score greater than Q30. The

alignment metrics of the BAM files from both pipelines were similar, with coverage

ranging from 66 to 363X vertically and 63 to 99.9% horizontally. Samples with low

coverage were resequenced. Approximately 8.3 thousand variants were identified by

the independent pipeline and 8.5 thousand by DNA Amplicon, stored in VCF files.

Although no statistically significant differences were observed in the overall analyses

between pipelines, the spreadsheet generated by DNA Amplicon had fewer artifacts

and more variants meeting the desired metrics for final clinical reports (DP > 20X

and approximately 50% allelic frequency). In the end, pathogenic mutations were

identified in 19.44% of probands (14/72), and probably pathogenic mutations in

2.78% (2/72), mainly in the BRCA1/2 genes. Additionally, VUS were found in 13.89%x

of probands (10/72), with a higher frequency in the ATM gene. Clinical reports were

released following minimum criteria for vertical (≥ 100X) and horizontal (global: 20X

≥ 90%; gene: 1X ≥ 90%) coverage. Projects like this strengthen the connection

between the university and society, providing a direct return to the community with

valuable data and information collected during scientific research.

BANKING MEMBERS:
Externa à Instituição - JULIA MARIA SARAIVA DUARTE - UFMG
Externo ao Programa - 3295713 - ISRAEL JOSE PEREIRA GARCIA
Presidente - 1457505 - LUCIANA LARA DOS SANTOS

Notícia cadastrada em: 23/11/2023 13:32