The Role of Med12 in Tumorigenesis
نویسندگان
چکیده
....................................................................................................... 8 REVIEW OF THE LITERATURE ................................................................ 10 1. Tumorigenesis ....................................................................................................................... 10 2. Genetics of cancer ................................................................................................................. 11 2.1 Genomic alterations ........................................................................................................ 12 2.2 Epigenetic and other changes in tumorigenesis ............................................................... 13 2.3 Cancer genes ................................................................................................................... 14 2.3.1 Oncogenes ................................................................................................................ 14 2.3.2 Tumor suppressor genes .......................................................................................... 15 2.3.3 Stability genes .......................................................................................................... 16 2.4 Inherited susceptibility for cancer ................................................................................... 16 2.5 Genome-wide methods in cancer genetics ...................................................................... 17 3. Uterine leiomyomas ............................................................................................................... 18 3.1 Development of uterine leiomyomas .............................................................................. 19 3.2 Chromosomal alterations in uterine leiomyomas ............................................................ 20 3.3 Hereditary leiomyomatosis and renal cell cancer syndrome ........................................... 21 3.4 MED12 mutations in uterine leiomyomas ....................................................................... 22 4. MED12 .............................................................................................................................. 23 4.1 MED12 as a subunit of the Mediator complex ................................................................ 25 4.2 MED12 in signaling pathways ........................................................................................ 27 4.3 MED12 mutations in the germ line ................................................................................. 28 4.4 Somatic MED12 mutations in other tumor types? .......................................................... 29 AIMS OF THE STUDY ................................................................................... 31 MATERIALS AND METHODS .................................................................... 32 1. Study subjects and samples .................................................................................................. 32 1.1 Tumor samples (I-V) ....................................................................................................... 32 1.2 Normal tissue samples (I-III) .......................................................................................... 35 1.3 Cell lines (II, V) .............................................................................................................. 35 2. Methods .................................................................................................................................. 36 2.1 Histopathological evaluation (I, III) ................................................................................ 36 2.2 DNA and RNA extraction (I-V) ...................................................................................... 36 2.3 Sanger sequencing (I-V) ................................................................................................. 37
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