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Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer.

ABSTRACT: More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of thyroid cancer, we performed a retrospective analysis of the formalin-fixed paraffin-embedded tumor samples from 50 patients who mainly displayed aggressive thyroid cancer using next-generation sequencing of 416 solid tumor-related genes. We adopted extensive bioinformatic analysis to vigorously remove germline single-nucleotide polymorphism and systematic sequencing errors, and report here that mutation in DNMT3A gene was significantly enriched in patients with PDTC or ATC.

SUBMITTER: Guo LC

PROVIDER: S-EPMC6370393 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer.

Guo Ling-Chuan LC Zhu Wei-Dong WD Ma Xiang-Yuan XY Ni Hao H Zhong En-Jian EJ Shao Yang W YW Yu Jie J Gu Dong-Mei DM Ji Shun-Dong SD Xu Hao-Dong HD Ji Cheng C Yang Jin-Ming JM Zhang Yi Y

Cancer biology & therapy 20180925 3

More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of th ...[more]

PMID: 30252567

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Project description:Estrogen receptor-? (ER-?), encoded by ESR1, is detected by immunohistochemistry in approximately 70% of invasive breast cancers and serves as a strong predictive biomarker. ESR1-activating mutations in the ligand-binding domain have been reported in up to 35-40% of ER-positive metastatic breast cancers and are associated with endocrine therapy resistance and disease progression. At present, it is unclear whether ESR1 mutations alter the immunohistochemical detection of ER performed in routine clinical practice. In this study, ESR1 mutations in breast cancer were identified utilizing Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a Food and Drug Administration-approved hybridization capture-based next-generation sequencing assay. Five hundred and eighty-six breast cancers from patients with locally advanced or metastatic disease were analyzed using MSK-IMPACT in the study period. ESR1 somatic alterations were identified in 67 breast cancer samples from 66 patients. Immunohistochemical analysis of ER, progesterone receptor, and human epidermal growth factor receptor 2 was performed on the primary and treated breast cancers from these patients at the time of diagnosis. Twenty unique ESR1 mutations were identified involving the ligand-binding domain, all in breast cancer samples from patients previously treated with endocrine therapy. The most frequent mutations were D538G (n?=?22), Y537S (n?=?7), and E380Q (n?=?7). All breast cancer samples with an ESR1 mutation were ER-positive by immunohistochemistry. Review of the ER immunohistochemistry in the paired untreated primary tumor and treated tumor from 34 patients showed no detectable change in the ER-positive immunohistochemical status (median percentage of invasive tumor cells with nuclear staining: untreated primary tumor 90%, treated tumor 95%). We conclude that ESR1 mutations do not appreciably diminish ER-positive staining by immunohistochemistry. In addition to standard biomarker testing by immunohistochemistry, the assessment of ESR1 mutations by molecular testing can help guide the clinical management of patients with ER-positive breast cancer in the setting of endocrine resistance and progression of disease.

Dataset Information

Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer.

Publications

Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer.

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