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Whole‐genome sequen...
Whole‐genome sequencing of synchronous thyroid carcinomas identifies aberrant DNA repair in thyroid cancer dedifferentiation
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- Paulsson, Johan O. (author)
- Karolinska Institutet
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- Backman, Samuel (author)
- Uppsala universitet,Experimentell kirurgi
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- Wang, Na (author)
- Karolinska Institutet
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- Stenman, Adam (author)
- Karolinska Institutet
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- Crona, Joakim (author)
- Uppsala universitet,Endokrin tumörbiologi
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- Thutkawkorapin, Jessada (author)
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
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- Ghaderi, Mehran (author)
- Karolinska Institutet
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- Tham, Emma (author)
- Karolinska Institutet
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- Stålberg, Peter (author)
- Uppsala universitet,Endokrinkirurgi
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- Zedenius, Jan (author)
- Karolinska Institutet
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- Juhlin, C. Christofer (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-11-29
- 2020
- English.
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 250:2, s. 183-194
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The genetics underlying thyroid cancer dedifferentiation is only partly understood and has not yet been characterised using comprehensive pan‐genomic analyses. We investigated a unique case with synchronous follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC), as well as regional lymph node metastases from the PDTC and ATC from a single patient using whole‐genome sequencing (WGS). The FTC displayed mutations in CALR, RB1, and MSH2, and the PDTC exhibited mutations in TP53, DROSHA, APC, TERT, and additional DNA repair genes – associated with an immense increase in sub‐clonal somatic mutations. All components displayed an overrepresentation of C>T transitions with associated microsatellite instability (MSI) in the PDTC and ATC, with borderline MSI in the FTC. Clonality analyses pinpointed a shared ancestral clone enriched for mutations in TP53‐associated regulation of DNA repair and identified important sub‐clones for each tumour component already present in the corresponding preceding lesion. This genomic characterisation of the natural progression of thyroid cancer reveals several novel genes of interest for future studies. Moreover, the findings support the theory of a stepwise dedifferentiation process and suggest that defects in DNA repair could play an important role in the clonal evolution of thyroid cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- thyroid carcinoma
- dedifferentiation
- whole-genome sequencing
- clonality
- DNA repair
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Paulsson, Johan ...
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Backman, Samuel
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Wang, Na
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Stenman, Adam
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Crona, Joakim
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Thutkawkorapin, ...
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show more...
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Ghaderi, Mehran
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Tham, Emma
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Stålberg, Peter
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Zedenius, Jan
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Juhlin, C. Chris ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Journal of Patho ...
- By the university
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Uppsala University
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Karolinska Institutet