Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Δευτέρα 1 Φεβρουαρίου 2016

Clonality analysis of multifocal papillary thyroid carcinoma by using genetic profiles

Abstract

Papillary thyroid carcinoma (PTC) is the most common adult thyroid malignancy and often presents with multiple anatomically distinct foci within the thyroid, known as multifocal papillary thyroid carcinoma (MPTC). The widespread application of the next-generation sequencing technologies in cancer genomics research provides novel insights into determining the clonal relationship between multiple tumours within the same thyroid gland. For eight MPTC patients, we performed whole-exome sequencing and targeted region sequencing to identify the non-synonymous point mutations and gene rearrangements of distinct and spatially separated tumour foci. Among these eight MPTCs, completely discordant mutational spectra were observed in the distinct cancerous nodules of patients MPTC1 and 5, suggesting that derivation of these nodules were from independent precursors. In another three cases (MPTC2, 6 and 8), the distinct MPTC foci of these patients had no other shared mutations except BRAF V600E, also indicating likely independent origins. Two patients (MPTC 3 and 4) shared almost identical mutational spectra amongst their separate tumour nodules, suggesting a common clonal origin. MPTC patient 7 had 7 cancer foci, of which 2 foci shared 66.7% of mutations, while the remaining cancer foci displayed no common non-synonymous mutations, indicating that MPTC7 has multiple independent origins accompanied by intraglandular disease dissemination.

In this study, we found that 75% of MPTC cases arose as independent tumours, which supports the field cancerization hypothesis describing multiple malignant lesions. MPTC may also arise from intra-thyroidal metastases from a single malignant clone, as well as multiple independent origins accompanied with intra-thyroidal metastasis.



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