@article{
author = "Milosevic, Zorica and Tanić, Nikola and Banković, Jasna Z. and Stankovic, Tijana and Buta, Marko and Lavrnic, Dragana and Milovanovic, Zorka and Pupic, Gordana and Stojković Burić, Sonja and Milinkovic, Vedrana and Ito, Yasuhiro and Džodić, Radan R.",
year = "2014",
abstract = "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.",
journal = "International Journal of Clinical and Experimental Pathology",
title = "Genetic alterations in quadruple malignancies of a patient with multiple
sclerosis: their role in malignancy development and response to therapy",
number = "4",
volume = "7",
pages = "1826-1833",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2290"
}