Abstract
Background
Thyroid cancer is one of the most common cancers in the world. Genetic factors are
important in the occurrence 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 causative 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 existence 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 predictive and valuable
for the familial heredity of thyroid cancer.
Keywords
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Article info
Publication history
Published online: May 07, 2022
Accepted:
March 29,
2022
Received:
April 22,
2021
Identification
Copyright
© 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
