A minimum set of markers was selected (levels of HMGA2 mRNA and miR-375, - 221, and -146b in combination with the mitochondrial-to-nuclear DNA ratio) and yielded highly accurate discrimination (sensitivity = 0.97; positive predictive value = 0.98) between goiters with benign tumors and malignant tumors and accurate typing of papillary, medullary, and Hürthle cell carcinomas.
PAX3, TGFB2 and HMGA2 were expressed predominantly in borderline/malignant PTs, but showed some expression in benign tumours; they may be important in the transition from the benign to borderline/malignant phenotype.
This analysis clearly demonstrates that as a rule, germ line mutations of HMGA2 are not the cause for benign tumors, e.g. uterine leiomyomas, or human malignant solid tumors.
The high-mobility group A2 (HMGA2) gene has a critical role in benign tumors where it is frequently rearranged, and in malignant tumors, where it is overexpressed in the absence of structural modification of the HMGA2 locus.
The lipoma preferred partner (LPP) gene is the most frequent translocation partner of HMGA2 in a subgroup of lipomas, which are benign tumors of adipose tissue.
Deregulation of the HMGA2 gene is a common molecular alteration implicated in the development of a variety of benign tumors, such as lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas.
This finding suggests a role for the HMGI-C gene also in the pathogenesis of this uncommon benign tumor type, in addition to its well-established role in the pathogenesis of common benign tumors such as lipomas, uterine leiomyomas, pulmonary chondroid hamartomas, and endometrial polyps.
Defects in the HMGI-C gene have been found in a variety of benign tumors, such as uterine leiomyomas, endometrial polyps, lipomas, and pulmonary chondroid hamartomas.
The results strongly suggest that pleomorphic adenomas are the only exception to the rule that entities of benign tumors with HMGIC rearrangements also have subtypes with HMGIY rearrangements.
Recently, the high mobility group protein gene, HMGIC, was identified as a common genetic denominator in benign tumors with chromosome 12q13-15 aberrations, such as lipomas, uterine leiomyomas, pleomorphic adenoma of the salivary glands, hamartomas of breast and lung, angiomyxomas, and endometrial polyps.
Our meta-analysis included eight eligible studies, with 428 ovarian cancers and 278 normal tissue samples and benign neoplasms. p16 promoter methylation was identified in 5.4 to 43.2% (median 27.86%) of ovarian cancers and 0 to 37.5% (median 15.8%) of normal tissue and benign neoplasms indicating that no significant association exists between p16 promoter methylation and epithelial ovarian cancer.
p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560).
The presence of BRAF V600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (e.g., p16 loss) in BRAF-driven oncogenesis.
Using a cutoff threshold based on receiver-operating characteristic analysis, 21 patients with ovarian cancer and three patients with benign tumors were considered positive for CDKN2A methylation while all patients with healthy ovaries were considered negative.
We propose that LMP1 acts at the early stages in carcinogenesis to promote the development of benign tumours and that early reduction of INK4a locus expression allows these lesions to expand in size.
Our results demonstrate that alterations of the INK4a-ARF locus are frequent and important events not only in the carcinogenesis of malignant, but also in benign tumors.