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Malignant tumours of the uterus and ovaries with Mullerian and germ cell or trophoblastic components have a somatic origin and are characterised by genomic instability
Author(s) -
Acosta Andres M,
Sholl Lynette M,
Cin Paola D,
Howitt Brooke E,
Otis Christopher N,
Nucci Marisa R
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14188
Subject(s) - biology , somatic cell , choriocarcinoma , germ cell , uterus , pathology , cancer research , genetics , medicine , gene
Aims Tumours of the female genital tract with a combination of malignant Mullerian and germ cell or trophoblastic tumour (MMGC/T) components are usually diagnosed in postmenopausal women, and pursue an aggressive clinical course characterised by poor response to therapy and early relapses. These clinical features suggest that MMGC/T are somatic in origin, but objective molecular data to support this interpretation are lacking. This study evaluates the molecular features of nine MMGC/T, including seven tumours containing yolk sac tumour (YST), one tumour containing choriocarcinoma and one tumour containing epithelioid trophoblastic tumour. The objectives were to: (i) investigate whether MMGC/T show a distinct genetic profile and (ii) explore the relationship between the different histological components. Methods and results Next‐generation sequencing of paired samples demonstrated that the mutational profile of the Mullerian and non‐Mullerian components of the tumour were almost identical in all cases. Moreover, the driver mutations identified were those expected in the specific subtype of Mullerian component present in each case. In contrast, variants expected in postpubertal germ cell tumours and gestational trophoblastic tumours were not identified, and FISH for i(12p) was negative in all cases tested. In this study, mismatch repair‐proficient MMGC/T (eight of nine) were characterised by a complex copy‐number variant profile, including numerous focal, regional, arm‐level and chromosome‐level events. Conclusions Comparison of paired samples supports that the YST and trophoblastic tumour components of MMGC/T have a somatic origin and often show numerous copy‐number variants, suggestive of underlying genomic instability.