Germline Mutations in Familial Papillary Thyroid Cancer

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Papillary thyroid cancer (PTC) is the most common thyroid malignancy, typically sporadic.
• Hereditary PTC accounts for approximately 5% of cases and is associated with earlier onset and increased risk of metastasis and recurrence.
• The genetic basis for the majority of hereditary PTC cases remains largely unknown.

Observation:

• This study investigated the genetic etiology of hereditary PTC in three Brazilian families.
• Whole exome sequencing (WES) was performed on probands, followed by genotyping of pathogenic/likely pathogenic sequence variants (P/LPSVs) in relatives.
• Seven P/LPSVs in seven distinct genes (ANXA3, NTN4, SERPINA1, FKBP10, PLEKHG5, P2RX5, SAPCD1) were identified.

Findings:

• Seven novel genes were found to harbor pathogenic/likely pathogenic sequence variants in hereditary PTC patients.
• These identified genes (ANXA3, NTN4, SERPINA1, FKBP10, PLEKHG5, P2RX5, SAPCD1) are potentially associated with the development of hereditary PTC.
• The specific variants identified include p.D283N*ANXA3, p.Y157S*NTN4, p.G172W*SERPINA1, p.G188S*FKBP10, p.R937C*PLEKHG5, p.L32Q*P2RX5, and p.Q76*SAPCD1.

Implications:

• The identified genes represent novel candidates for the molecular basis of hereditary PTC.
• Further research and validation in larger cohorts of hereditary PTC families are necessary to confirm these findings.
• This study provides a foundation for understanding the genetic landscape of inherited thyroid cancer and may inform future diagnostic and therapeutic strategies.