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Targeted DNA Sequencing Detects Mutations Related to Susceptibility among Familial Non-medullary Thyroid Cancer.

Yu Y, Dong L, Li D, Chuai S, Wu Z, Zheng X, Cheng Y, Han L, Yu J, Gao M - Sci Rep (2015)

Bottom Line: Using next-generation sequencing we performed deep sequencing to achieve 500× coverage of the targeted regions.At the end 45 variants were identified in 29 of 47 familial patients and 6 of 16 sporadic patients.The findings would also provide insights on monitoring the potential second cancers for thyroid cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.

ABSTRACT
Some studies have demonstrated that familial non-medullary thyroid cancer (FNMTC) has a more aggressive clinical behavior compared to sporadic NMTC (SNMTC). However, FNMTC is difficult to differentiate from SNMTC by the morphology and immunohistochemistry. Although genes responsible for FNMTC were unclear, screening for rare germline mutations on known important tumor suppressor genes might offer more insights on predicting susceptibility to FNMTC. Here, a customized panel was designed to capture all exons of 31 cancer susceptive genes possibly related to FNMTC. Using next-generation sequencing we performed deep sequencing to achieve 500× coverage of the targeted regions. At the end 45 variants were identified in 29 of 47 familial patients and 6 of 16 sporadic patients. Notably, several germline mutations were found matching between paired FNMTC patients from the same family, including APC L292F and A2778S, BRAF D22N, MSH6 G355S and A36V, MSH2 L719F, MEN1 G508D, BRCA1 SS955S, BRCA2 G2508S, and a GNAS inframe insertion. We demonstrated a novel approach to help diagnose and elucidate the genetic cause of the FNMTC patients, and assess whether their family members are exposed to a higher genetic risk. The findings would also provide insights on monitoring the potential second cancers for thyroid cancer patients.

No MeSH data available.


Related in: MedlinePlus

Base change distribution of all SNVs and distribution of MAF.(a) Base substitution distribution of all single-nucleotide variants (SNVs) across all samples. (b) The distribution of the minor allele frequencies (MAF) across all identified variants.
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f3: Base change distribution of all SNVs and distribution of MAF.(a) Base substitution distribution of all single-nucleotide variants (SNVs) across all samples. (b) The distribution of the minor allele frequencies (MAF) across all identified variants.

Mentions: We applied GATK 3.2 for genotyping the two batches of samples and identified 8462 single-nucleotide variants (SNVs) and 1699 insertion/deletion (INDELs) overall. The base substitution pattern is highly consistent across all samples (Fig. 3a), with an average transition-transversion (ti/tv) ratio of 2.55, similar to previously reported ti/tv ratio among exome regions. We then plotted the distribution of the minor allele frequencies (MAF) across all identified variants (Fig. 3b). The MAF demonstrates a clear bi-modal distribution, peaking at 0.5 and 1, a distribution expected for germline variants.


Targeted DNA Sequencing Detects Mutations Related to Susceptibility among Familial Non-medullary Thyroid Cancer.

Yu Y, Dong L, Li D, Chuai S, Wu Z, Zheng X, Cheng Y, Han L, Yu J, Gao M - Sci Rep (2015)

Base change distribution of all SNVs and distribution of MAF.(a) Base substitution distribution of all single-nucleotide variants (SNVs) across all samples. (b) The distribution of the minor allele frequencies (MAF) across all identified variants.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4632085&req=5

f3: Base change distribution of all SNVs and distribution of MAF.(a) Base substitution distribution of all single-nucleotide variants (SNVs) across all samples. (b) The distribution of the minor allele frequencies (MAF) across all identified variants.
Mentions: We applied GATK 3.2 for genotyping the two batches of samples and identified 8462 single-nucleotide variants (SNVs) and 1699 insertion/deletion (INDELs) overall. The base substitution pattern is highly consistent across all samples (Fig. 3a), with an average transition-transversion (ti/tv) ratio of 2.55, similar to previously reported ti/tv ratio among exome regions. We then plotted the distribution of the minor allele frequencies (MAF) across all identified variants (Fig. 3b). The MAF demonstrates a clear bi-modal distribution, peaking at 0.5 and 1, a distribution expected for germline variants.

Bottom Line: Using next-generation sequencing we performed deep sequencing to achieve 500× coverage of the targeted regions.At the end 45 variants were identified in 29 of 47 familial patients and 6 of 16 sporadic patients.The findings would also provide insights on monitoring the potential second cancers for thyroid cancer patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.

ABSTRACT
Some studies have demonstrated that familial non-medullary thyroid cancer (FNMTC) has a more aggressive clinical behavior compared to sporadic NMTC (SNMTC). However, FNMTC is difficult to differentiate from SNMTC by the morphology and immunohistochemistry. Although genes responsible for FNMTC were unclear, screening for rare germline mutations on known important tumor suppressor genes might offer more insights on predicting susceptibility to FNMTC. Here, a customized panel was designed to capture all exons of 31 cancer susceptive genes possibly related to FNMTC. Using next-generation sequencing we performed deep sequencing to achieve 500× coverage of the targeted regions. At the end 45 variants were identified in 29 of 47 familial patients and 6 of 16 sporadic patients. Notably, several germline mutations were found matching between paired FNMTC patients from the same family, including APC L292F and A2778S, BRAF D22N, MSH6 G355S and A36V, MSH2 L719F, MEN1 G508D, BRCA1 SS955S, BRCA2 G2508S, and a GNAS inframe insertion. We demonstrated a novel approach to help diagnose and elucidate the genetic cause of the FNMTC patients, and assess whether their family members are exposed to a higher genetic risk. The findings would also provide insights on monitoring the potential second cancers for thyroid cancer patients.

No MeSH data available.


Related in: MedlinePlus