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Genetic analysis of a morphologically heterogeneous ovarian endometrioid carcinoma
Author(s) -
Geyer Felipe C,
Pareja Fresia,
Burke Kathleen A,
Schultheis Anne M,
Hussein Yaser R,
Ye Jiqing,
De Filippo Maria R,
Marchio Caterina,
Macedo Gabriel S,
Piscuoglio Salvatore,
Lim Raymond S,
Toy Eugene,
Murali Rajmohan,
Jungbluth Achim A,
ReisFilho Jorge S,
Soslow Robert A,
Weigelt Britta
Publication year - 2017
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.13240
Subject(s) - biology , massive parallel sequencing , carcinoma , somatic cell , cancer research , sanger sequencing , ovarian cancer , ovarian carcinoma , clear cell , mutation , gene , dna sequencing , cancer , genetics
Aims Low‐grade ovarian endometrioid carcinomas may be associated with high‐grade components. Whether the latter are clonally related to and originate from the low‐grade endometrioid carcinoma remains unclear. The aim of this study was to use massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low‐grade and high‐grade components. Methods and results DNA samples extracted from each tumour component (low‐grade endometrioid, high‐grade anaplastic and high‐grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing with the 410‐gene Memorial Sloan Kettering‐Integrated Mutation Profiling of Actionable Cancer Targets ( MSK ‐ IMPACT ) sequencing assay. Somatic single nucleotide variants, small insertions and deletions, and copy number alterations were detected with state‐of‐the‐art bioinformatics algorithms, and validated with orthogonal methods. The endometrioid carcinoma and the associated high‐grade components shared copy number alterations and four clonal mutations, including SMARCA 4 mutations, which resulted in loss of BRG 1 protein expression. Subclonal mutations and mutations restricted to single components were also identified, such as distinct TP 53 mutations restricted to each histological component. Conclusions Histologically distinct components of ovarian endometrioid carcinomas may show intratumour genetic heterogeneity but be clonally related, harbouring a complex clonal composition. In the present case, SMARCA 4 mutations were probably early events, whereas TP 53 somatic mutations were acquired later in evolution.