The Driver Mutational Landscape of Ovarian Squamous Cell Carcinomas Arising in Mature Cystic Teratoma

Abstract

We sought to identify the genomic abnormalities in squamous cell carcinomas (SCC) arising in ovarian mature cystic teratoma (MCT), a rare gynecological malignancy of poor prognosis. We performed copy number, mutational state, and zygosity analysis of 151 genes in SCC arising in MCT ( = 25) using next-generation sequencing. The presence of high-/intermediate-risk HPV genotypes was assessed by quantitative PCR. Genomic events were correlated with clinical features and outcome. MCT had a low mutation burden with a mean of only one mutation per case. Zygosity analyses of MCT indicated four separate patterns, suggesting that MCT can arise from errors at various stages of oogenesis. A total of 244 abnormalities were identified in 79 genes in MCT-associated SCC, and the overall mutational burden was high (mean 10.2 mutations per megabase). No SCC was positive for HPV. The most frequently altered genes in SCC were (20/25 cases, 80%), (13/25 cases, 52%), and (11/25 cases, 44%). Mutation in was associated with improved overall survival. In 8 of 20 cases with mutations, two or more variants were identified, which were bi-allelic. Ovarian SCC arising in MCT has a high mutational burden, with mutation the most common abnormality. The presence of mutation is a good prognostic factor. SCC arising in MCT share similar mutation profiles to other SCC. Given their rarity, they should be included in basket studies that recruit patients with SCC of other organs. .

Recurrence of ovarian squamous cell carcinoma with MET gene copy number variation: a case report and review of literature

“…[19,23] On the contrary, Cooke et al found no SCC was positive for HPV in their 25 cases. [20] In our case, we also can find diffusely positive for p16 in immunohistochemical staining while her was HPV negative. More validation studies were needed to explore whether HPV might have acted as the root cause for the malignant transformation in OMCT.…”

XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary

“…Squamous cell carcinoma (SCC) is the most common histological type in malignant transformation of MCT [1,3], which is reasonable because skin epithelium is usually found in MCT [4]. Recently, Cooke et al analyzed genomic alterations of 25 SCCs arising from MCT (MCT-SCC) by using a gene panel with 151 cancer-related genes and reported frequent alterations of TP53, PIK3CA, and CDKN2A that are also frequently detected in other types of SCC [5]. However, the number of targeted genes in their study was limited, and other molecular characteristics of MCT-SCC such as transcriptome, proteome, and methylation profiles remain unclear.…”

Recurrence of ovarian squamous cell carcinoma with MET gene copy number variation: a case report and review of literature

“…The most frequently altered genes in SCC were TP53 (20/25 cases, 80%), PIK3CA (13/25 cases, 52%) and CDKN2A (11/25 cases, 44%). [20] In the study done by Iwasa et al, [21] overexpression of the p53 protein was observed in 67% SCC cases (14 in 21 cases), while four of them had point mutations in the p53. In humans, p16 is encoded by the CDKN2A gene.…”