Identification of individuals at high-risk for cancer can help cancer prevention, early detection and can guide cancer treatment. Novel methods to identify patients with germline mutations could help conventional genetic cancer risk assessment. Germline mutation detection in the context of tumor genomic sequencing has been reported in single-institution and retrospective consortia setting, such as the Cancer Genome Atlas. These studies have demonstrated that somatic genotyping may be a potential resource.
There are no studies that have investigated germline cancer predisposition in thyroid fine needle aspiration (FNA) biopsy samples. However, somatic genotyping of thyroid FNA samples may be certainly a potential resource. Indeed, during the past several years, several molecular tests have been developed to reduce the diagnostic uncertainty of indeterminate thyroid fine-needle aspirations and they are now being used more increasingly.
Aim of this study was to describe incidental germline mutations identified through in-house FNA testing of thyroid nodule patients who underwent somatic genotyping in our institution.
Preliminary data were already obtained. FNA thyroid samples (N=123) from 117 patients with thyroid nodules were previously tested for mutations in thyroid cancer drivers using targeted next-generation sequencing (NGS). NGS data will be analyzed by bioinformatics analysis in order to select putative germline variants. Germline status of each variant will be finally confirmed by Sanger sequencing analysis on normal thyroid tissue from each thyroid nodule patient who underwent surgery. The proportion of pathogenic hereditary variants in the whole cohort will be assessed.
An important benefit of cancer predisposition gene (CPG) testing is being able to provide information about cancer risks to relatives. One of the unusual characteristics of CPGs is their capacity to serve as a biomarker of future disease. Identifying a CPG mutation can provide opportunity to implement surveillance and/or risk-reducing measures that mitigate or prevent cancer. The presumption is that if a cancer is detected early, treatment and survival will be improved. Germline mutation detection in the context of tumor genomic sequencing has been reported in single-institution and retrospective consortia setting, such as the Cancer Genome Atlas. These studies have demonstrated that somatic genotyping may be a potential resource. Novel methods to identify patients with germline mutations could help conventional genetic cancer risk assessment, with the enrollment of at-risk patients and their family members in routine follow-up.
There are no studies that have investigated germline cancer predisposition in fine needle aspiration samples from thyroid nodules patients. However, somatic genotyping of thyroid FNA biopsy samples may be certainly a potential resource. Indeed, during the past several years, several molecular tests have been developed to reduce the diagnostic uncertainty of indeterminate thyroid fine-needle aspirations and they are now being used more increasingly. A custom thyroid cancer panel has been developed also in our laboratory and to date we have analyzed more than 100 thyroid FNA biopsy samples. The incidence of germline, rare and pathogenic variants will be investigated in this cohort.