A novel truncated form of HMGA2 in tumors of the ovaries

Abstract

Abstract. Neoplasms of the ovary are the second most common tumor of the female reproductive system, and the most lethal of the gynecological malignancies. Ovarian tumors are divided into a copious number of different groups reflecting their different features. The present study analyzed 187 ovarian tumors (39 sex-cord stromal tumors, 22 borderline tumors and 126 carcinomas) for the expression of the high-mobility group AT-hook 2 (HMGA2) gene, for mutations in the isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1), isocitrate dehydrogenase (NADP(+)) 2, mitochondrial (IDH2) and telomerase reverse transcriptase (TERT) genes, and for methylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter. Reverse transcription-polymerase chain reaction analysis showed that HMGA2 was expressed in 74.5% of the samples (120/161). A truncated transcript of HMGA2 was identified in 11 cases. A novel truncated form of HMGA2 was found in 4 serous high-grade carcinomas. Only 4 tumors (4/185) showed the TERT C228T mutation. No IDH1 or IDH2 mutations were found. Methylation of the promoter of MGMT was found in 2 borderline tumors (2/185). HMGA2 was expressed, in its truncated and native form, in different ovarian tumors, even the less aggressive types, underscoring the general importance of this gene in ovarian tumorigenesis. Mutations involving TERT, as well as MGMT promoter methylation, are rare events in ovarian tumors. IntroductionTumors of the ovaries account for 30% of all cancers of the female genital system; they are a heterogeneous group of neoplasms, divided into a number of different subgroups, depending largely on histological and cytological features (1).The majority (90%) of ovarian tumors are epithelial in nature. Malignant epithelial ovarian tumors are currently divided into high-grade serous, low-grade serous, endometrioid, mucinous and clear cell carcinomas (2).Borderline tumors of the ovary are neoplasms of low malignant potential. These tumors present with cellular atypia, but are not invasive. A few of these tumors share genomic and molecular features with carcinomas (3), but it remains unclear as to whether this is a feature of only a subset or of borderline tumors in general.Sex-cord stromal tumors account for 8% of all ovarian tumors and are further classified based on their predominant cell content; for example, granulosa cell tumors contain ≥10% granulosa cells. The thecoma-fibroma group of tumors is dominated by theca cells (thecoma), stromal fibroblasts (fibroma) or the two cell types in different proportions (thecofibroma) (4).Heterogeneity among ovarian tumors biologically and clinically represents a considerable challenge. The molecular and genetic profiles of the tumors could aid in predicting their inherent aggressiveness and could also provide keys to more specific treatments. As a contribution toward this goal, the present study analyzed 187 samples of different types of ovarian tumors, namely, granulosa cell tumors, thecofibromas, fibromas, teratomas, borderline tumors and infiltrat...

Association of MGMT promoter methylation with tumorigenesis features in patients with ovarian cancer: A systematic meta‐analysis

“…Our initial search yielded a total of 81 potential studies based on the above described search strategy. In the end, 10 case–control studies involving 910 ovarian tissue samples (Agostini et al., ; An et al., ; Brait et al., ; Chmelarova et al., ; Furlan et al., ; Makarla et al., ; Rimel, Huettner, Powell, Mutch, & Goodfellow, ; Roh et al., ; Shilpa et al., ; Wu et al., ) were included in the current meta‐analysis (Figure ). The main characteristics of eligible studies were extracted and shown in Table .…”

“…The methylation frequency of MGMT promoter was found to be different in this study. The methylation rate of MGMT promoter ranged from 0% (Agostini et al., ) to 38.9% (Furlan et al., ) in ovarian carcinoma. MGMT promoter methylation had a different methylation frequency in LMP samples, with a variation in 0% (Makarla et al., ) to 28.6% (Shilpa et al., ).…”

“…No methylation rate of the MGMT promoter was detected in patients with ovarian carcinoma by Agostini et al. (Agostini et al., ). However, An et al.…”

“…Nevertheless, data with regard to the methylation levels of the MGMT promoter were inconsistent in ovarian cancer. No methylation rate of the MGMT promoter was detected in patients with ovarian carcinoma by Agostini et al (Agostini et al, 2016). However, An et al reported that MGMT promoter methylation had a high rate in ovarian cancer .…”

Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian tumors: implications for HMGA2 expression

“…In a previous study [7], we found HMGA2 expressed in 74% of the ovarian tumors examined. We have now quantified the expression of this gene in the same series of tumors.…”