Ali S Alzahrani1,2,3, Avaniyapuram Kannan Murugan1, Ebtesam Qasem1, Hindi Al-Hindi4. 1. 1 Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia . 2. 2 Department of Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia . 3. 3 Department of Research Center-Jeddah, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia . 4. 4 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia .
Abstract
BACKGROUND: Familial non-medullary thyroid cancer (NMTC) occurs either as part of known hereditary syndromes or as a non-syndromic isolated hereditary tumor. Although the genes underlying the syndromic type of NMTC have been identified in most syndromes, no clear underlying gene has been identified in the non-syndromic NMTC. Recently, a c.1601G>A, p.G534E mutation in the HABP2 gene was reported to be the underlying genetic defect in a family with seven members affected by NMTC. The G534E variant has also been reported to occur in about 4.7% of cases of the Thyroid Cancer Genome Atlas (TCGA) database. OBJECTIVES: The aim of this study was to explore whether the recent finding of G534E genetic variant can be replicated in a large sample of NMTC, including 11 members of four unrelated families with familial NMTC and 509 cases of sporadic pediatric (63 cases) and adult NMTC (446 cases). METHODS: All exons and exon-intron boundaries of HABP2 were screened in 11 members of four families with familial non-syndromic NMTC using DNA isolated from peripheral leucocytes, polymerase chain reaction, and direct sequencing. The G534E variant was also screened for specifically in 229 cases of sporadic NMTC using DNA isolated from peripheral leucocytes and an additional 217 cases of NMTC using DNA isolated from formalin-fixed paraffin-embedded tumor tissues. As a control cohort, 190 healthy individuals without known thyroid disease were also studied for the presence of the G534E variant using DNA isolated from peripheral leucocytes. RESULTS: None of the familial NMTC carried HABP2 mutations. Of 509 sporadic NMTC, only one case (0.2%) harbored the G534E variant. Similarly, only one case (0.5%) of the control group harbored the G534E variant. CONCLUSION: In this study, HABP2 mutations were not found in familial NMTC, and the G534E variant is not the underlying genetic defect in a large sample of sporadic NMTC from the Middle East.
BACKGROUND: Familial non-medullary thyroid cancer (NMTC) occurs either as part of known hereditary syndromes or as a non-syndromic isolated hereditary tumor. Although the genes underlying the syndromic type of NMTC have been identified in most syndromes, no clear underlying gene has been identified in the non-syndromic NMTC. Recently, a c.1601G>A, p.G534E mutation in the HABP2 gene was reported to be the underlying genetic defect in a family with seven members affected by NMTC. The G534E variant has also been reported to occur in about 4.7% of cases of the Thyroid Cancer Genome Atlas (TCGA) database. OBJECTIVES: The aim of this study was to explore whether the recent finding of G534E genetic variant can be replicated in a large sample of NMTC, including 11 members of four unrelated families with familial NMTC and 509 cases of sporadic pediatric (63 cases) and adult NMTC (446 cases). METHODS: All exons and exon-intron boundaries of HABP2 were screened in 11 members of four families with familial non-syndromicNMTC using DNA isolated from peripheral leucocytes, polymerase chain reaction, and direct sequencing. The G534E variant was also screened for specifically in 229 cases of sporadic NMTC using DNA isolated from peripheral leucocytes and an additional 217 cases of NMTC using DNA isolated from formalin-fixed paraffin-embedded tumor tissues. As a control cohort, 190 healthy individuals without known thyroid disease were also studied for the presence of the G534E variant using DNA isolated from peripheral leucocytes. RESULTS: None of the familial NMTC carried HABP2 mutations. Of 509 sporadic NMTC, only one case (0.2%) harbored the G534E variant. Similarly, only one case (0.5%) of the control group harbored the G534E variant. CONCLUSION: In this study, HABP2 mutations were not found in familial NMTC, and the G534E variant is not the underlying genetic defect in a large sample of sporadic NMTC from the Middle East.
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