Mirjana Magic - Academia.edu (original) (raw)
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Papers by Mirjana Magic
BMC Cancer, 2010
Background: Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thu... more Background: Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort.
BMC Cancer, 2010
Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring... more Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect.
Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 2009
Increasing number of publications in the last 10 years implicated that cancer development depends... more Increasing number of publications in the last 10 years implicated that cancer development depends, except genetic alterations, also on inheritable gene expression patterns that are not bound to DNA sequence alterations. These epigenetic mechanisms manifest mostly through changes in chromatin packing and in localized gene promoter changes that influence the transcription of the genes involved in carcinogenesis. These changes are mitoticaly inheritable and potentially reversible, providing large possibilities of epigenetic therapy of cancer. So far this therapy lacks specificity of targeting certain genes. Instead, epigenetic therapy attempts either to reactivate or to silence genes that are important for the cancer progress. Epigenetic therapy of cancer is based mostly on the usage of inhibitors of DNA methyltransferases (DNMTs), histone deacetylase (HDAC) inhibitors and anti-micro-RNA therapy. Developments that involve integration of the latest technological advances, such as whole ...
BMC Cancer, 2010
Background: Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thu... more Background: Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort.
BMC Cancer, 2010
Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring... more Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect.
Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 2009
Increasing number of publications in the last 10 years implicated that cancer development depends... more Increasing number of publications in the last 10 years implicated that cancer development depends, except genetic alterations, also on inheritable gene expression patterns that are not bound to DNA sequence alterations. These epigenetic mechanisms manifest mostly through changes in chromatin packing and in localized gene promoter changes that influence the transcription of the genes involved in carcinogenesis. These changes are mitoticaly inheritable and potentially reversible, providing large possibilities of epigenetic therapy of cancer. So far this therapy lacks specificity of targeting certain genes. Instead, epigenetic therapy attempts either to reactivate or to silence genes that are important for the cancer progress. Epigenetic therapy of cancer is based mostly on the usage of inhibitors of DNA methyltransferases (DNMTs), histone deacetylase (HDAC) inhibitors and anti-micro-RNA therapy. Developments that involve integration of the latest technological advances, such as whole ...