Cathepsin F genetic mutation is associated with familial papillary thyroid cancer

Background: Thyroid cancer is one of the most common cancers in the world. Genetic factors are important in the occur-rence and development of thyroid cancer, and genetic diagnosis has become an important basis for the prognosis of benign and malignant nodules. We identify a family of six siblings with inherited thyroid cancer susceptibility. All six members of this generation have been definitely diagnosed with papillary thyroid carcinoma. This work aims at confirming the relevant causa-tive genes for thyroid cancer in this pedigree.Methods: We extract DNA from the peripheral blood of six individuals and perform whole genome sequencing. Sanger sequencing and immunohistochemistry further testify the cathepsin F (CTSF) mutation and expression.Results: We identify 57 single nucleotide variations (SNVs) out of at least 4 affected family members via certain filter criteria. The CTSF gene found in five of the six family members is here considered the most promising candidate gene mutation for familial thyroid cancer. Besides, our research also proves several known genes including CTSB, TEKT4, ESR1, MSH6, DIRC3, GNAS, and BANCR that act as probable oncogenic drivers in this family. The Sanger sequencing identifies the exis-tence and veracity of CTSF somatic mutations. The CTSF immunohistochemistry of thyroid cancer tissue specimens displays that higher CTSF expression in mutated patients than that in wild-type patient as well as pericarcinomatous tissue.Conclusions: We conclude that the evaluation of CTSF gene mutations of patients in thyroid cancer families may be predic-tive and valuable for the familial heredity of thyroid cancer.

Automated summary

The study conducted whole genome sequencing on a family of six siblings with inherited thyroid cancer susceptibility, identifying CTSF gene as the most promising candidate gene mutation for familial thyroid cancer. Additionally, several known oncogenic driver genes were also recognized. The evaluation of CTSF gene mutations in thyroid cancer patients may be predictive and valuable for familial heredity of thyroid cancer.