Genetic alterations in quadruple malignancies of a patient with multiple sclerosis: their role in malignancy development and response to therapy
| Autor: | Milosevic, Z., Tanic, N., Bankovic, J., Stankovic, T., Buta, M., Lavrnic, D., Milovanovic, Z., Pupic, G., Stojkovic, S., Milinkovic, V., Ito, Y., Radan Dzodic |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Multiple Sclerosis Case Report Bone Neoplasms Breast Neoplasms Quadruple cancers multiple sclerosis Proto-Oncogene Proteins p21(ras) Proto-Oncogene Proteins Azathioprine Humans Thyroid Neoplasms Melanoma Cyclin-Dependent Kinase Inhibitor p16 Carcinoma Ductal Breast Proto-Oncogene Proteins c-ret PTEN Phosphohydrolase Combined Modality Therapy Carcinoma Papillary Neoplasm Proteins Carcinoma Medullary Mutation ras Proteins Female Tumor Suppressor Protein p53 Immunosuppressive Agents |
| Zdroj: | Scopus-Elsevier Europe PubMed Central International Journal of Clinical and Experimental Pathology |
| Popis: | Multiple cancers represent 2.42\% of all human cancers and are mainly double or triple cancers. Many possible causes of multiple malignancies have been reported such as genetic alterations, exposure to anti-cancer chemotherapy, radiotherapy, immunosuppressive therapy and reduced immunologic response. We report a female patient with multiple sclerosis and quadruple cancers of different embryological origin. Patient was diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma (MTC), multicentric micropapillary thyroid carcinoma, scapular and lumbar melanomas (Clark II, Breslow II), and lobular invasive breast carcinoma (T1a, NO, MO). All tumors present in our patient except micropapillary thyroid carcinomas were investigated for gene alterations known to have a key role in cancer promotion and progression. Tumor samples were screened for the p16 alterations (loss of heterozygosity and homozygous deletions), loss of heterozygosity of PTEN, p53 alterations (mutational status and loss of heterozygosity) and mutational status of RET, HRAS and KRAS. Each type of tumor investigated had specific pattern of analyzed genetic alterations. The most prominent genetic changes were mutual alterations in PTEN and p53 tumor suppressors present in breast cancer and two melanomas. These co-alterations could be crucial for promoting development of multiple malignancies. Moreover the insertion in 4th codon of HRAS gene was common for all tumor types investigated. It represents frameshift mutation introducing stop codon at position 5 which prevents synthesis of a full-length protein. Since the inactivated RAS enhances sensitivity to tamoxifen and radiotherapy this genetic alteration could be considered as a good prognostic factor for this patient. Ministry of Education, Science and Technological Development of the Republic of Serbia {[}III41031] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|