Somatic genetic alterations in synchronous and metachronous low-grade serous tumours and high-grade carcinomas of the adnexa Journal Article
| Authors: | Murali, R.; Selenica, P.; Brown, D. N.; Cheetham, R. K.; Chandramohan, R.; Claros, N. L.; Bouvier, N.; Cheng, D. T.; Soslow, R. A.; Weigelt, B.; McCluggage, W. G. |
| Article Title: | Somatic genetic alterations in synchronous and metachronous low-grade serous tumours and high-grade carcinomas of the adnexa |
| Abstract: | Aims: Low-grade serous carcinomas (LGSCs) and their precursors serous borderline tumours (SBTs) characteristically harbour mutations in BRAF, KRAS or NRAS but rarely in TP53, whereas high-grade serous carcinomas (HGSCs) are characterised by frequent TP53 mutations but rare BRAF, KRAS or NRAS mutations. In a small subset of cases, LGSCs and/or SBTs develop into high-grade tumours, including HGSCs and poorly differentiated carcinomas (PDCs). Here, we sought to define the repertoire of somatic genetic alterations in low-grade serous tumours and synchronous or metachronous high-grade adnexal carcinomas. Methods and results: DNA extracted from five SBTs/LGSCs and synchronous or metachronous HGSCs/PDCs and matched normal tissue was subjected to massively parallel sequencing targeting all exons and selected non-coding regions of 341 cancer-related genes. The low-grade and high-grade tumours from a given case were related, and shared mutations and copy number alterations. Progression from low-grade to high-grade lesions was observed, and involved the acquisition of additional mutations and/or copy number alterations, or shifts from subclonal to clonal mutations. Only two (an HGSC and a PDC) of the five high-grade tumours investigated harboured TP53 mutations, whereas NRAS and KRAS hotspot mutations were seen in two HGSCs and one HGSC, respectively. Conclusions: Our results suggest that progression from SBT to HGSC may take place in a subset of cases, and that at least some of the rare HGSCs lacking TP53 mutations may be derived from a low-grade serous precursor. © 2018 John Wiley & Sons Ltd |
| Keywords: | molecular genetics; ovary; massively parallel sequencing; high-grade serous carcinoma; low-grade serous carcinoma; serous borderline tumour; tumour progression |
| Journal Title: | Histopathology |
| Volume: | 74 |
| Issue: | 4 |
| ISSN: | 0309-0167 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2019-03-01 |
| Start Page: | 638 |
| End Page: | 650 |
| Language: | English |
| DOI: | 10.1111/his.13796 |
| PUBMED: | 30565721 |
| PROVIDER: | scopus |
| PMCID: | PMC6626549 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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