Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma
نویسندگان
چکیده
Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively.
منابع مشابه
Metastatic Renal cell Carcinoma Presenting as a clear-cell Tumor in Tongue: A Case Report
Introduction: Metastatic lesions of the oral cavity are extremely rare, accounting for approximately 1% of all malignant oral tumors. The most common primary sources of metastatic tumors in the oral region are, from the most to the least common, the breast, lung, kidney, bone, and colon. Renal cell carcinoma accounts for nearly 3% of all adult malignancies. It usually metastasizes to the lungs,...
متن کاملDownregulation of TMEM40 by miR-138-5p suppresses cell proliferation and mobility in clear cell renal cell carcinoma
Background: Clear cell renal cell carcinoma (ccRCC) represents approximately 70% of RCC,as the most frequent histological subtype of RCC. MiR-138-5p, a tumor-related microRNA (miRNA), has been reported to be implicated in the diverse types of human malignancies, but its role in ccRCCremains unclear. Objective: The study was designed to investigate the function...
متن کاملP-88: Comparing Epigenetic Profile of Oct4 Regulatory Region in Embryonal Carcinoma Cells under Retinoic Acid Induction
Background: Embryonal carcinoma (EC) cells derived from germ cell tumors are valuable tools for investigating differentiation and developmental biology processes in vitro. The advantage of the reproducible and rapid expansion of these cell lines provides a useful alternative to embryos for the study of mammalian cell differentiation. During early stages of cell differentiation, the rate of tran...
متن کاملThree cases of pleural metastasis of renal clear cell carcinoma diagnosis: cases report
Background: Malignant pleural effusion is common in patients with advanced malignant tumor. The aim of this study is to analyze the characteristics of pleural metastasis of renal clear cell carcinoma, pleural effusion under medical thoracoscopy and the diagnostic value of interventional thoracoscopy-guided biopsy, and to improve the understanding of pleural metastasis of renal clear cell carcin...
متن کاملA Rare Case of Metastasis of Renal Clear Cell Carcinoma to the Thyroid Gland, Presenting as a Goiter Nodule, Three Years After Nephrectomy
Thyroid gland metastatic tumors are rare in clinical practice. Clear cell RCC is one of common metastatic tumors to thyroid. We here reported a case of incidentally found clear cell renal carcinoma metastasis to the thyroid gland 3 years after nephrectomy, in the thyroidectomy procedure performed for the patient due to the thyroid enlargement caused by multinodular goiter. A 65-year-old Iranian...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2017