Bora Baysal | Roswell Park Cancer Institute (original) (raw)

Papers by Bora Baysal

Research paper thumbnail of Additional file 6: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S5. C>U RNA editing events shared between NK cells and 293T/APOBEC3A, and NK cells, 293T... more Table S5. C>U RNA editing events shared between NK cells and 293T/APOBEC3A, and NK cells, 293T/APOBEC3A and 293T/APOBEC3G overexpression systems. (XLSX 14 kb)

Research paper thumbnail of Additional file 4: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S3. C>U RNA editing events after the third filter (stem-loop). These events are located ... more Table S3. C>U RNA editing events after the third filter (stem-loop). These events are located at the 3â ˛-end of loops in putative stem-loop structures within exons or UTRs. (XLSX 59 kb)

Research paper thumbnail of Additional file 3: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S2. C>U RNA editing events after the second filter (− 1 C or T). These events have C or ... more Table S2. C>U RNA editing events after the second filter (− 1 C or T). These events have C or T at − 1 nucleotide position. (XLSX 222 kb)

Research paper thumbnail of Additional file 2: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S1. C>U RNA editing events after the first filter (FDRâ

Research paper thumbnail of Additional file 1: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Figure S1-S12. Supplementary figures. (PPTX 1499 kb)

Research paper thumbnail of Additional file 10: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S9. Oligonucleotide primer sequences used for PCR amplification and Sanger sequencing. (XLS... more Table S9. Oligonucleotide primer sequences used for PCR amplification and Sanger sequencing. (XLSX 10 kb)

Research paper thumbnail of Additional file 9: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S8. Gene expression levels in normoxic and hypoxic NK cells. (XLSX 3002 kb)

Research paper thumbnail of Additional file 8: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S7. Evolutionary conservation analysis of all non-synonymous C>U RNA editing sites. (XLS... more Table S7. Evolutionary conservation analysis of all non-synonymous C>U RNA editing sites. (XLSX 18 kb)

Research paper thumbnail of Additional file 7: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S6. A>I RNA editing events in RADAR database that are induced by hypoxia in NK cells. (X... more Table S6. A>I RNA editing events in RADAR database that are induced by hypoxia in NK cells. (XLSX 11 kb)

Research paper thumbnail of Natural selection increases mutational robustness in complex diseases: Mendelian evidence from early versus late onset common diseases

Background. Natural selection operates on genetically influenced phenotypic variations that confe... more Background. Natural selection operates on genetically influenced phenotypic variations that confer differential survival or reproductive advantages. Common diseases are frequently associated with increased mortality and disability and complex heritable factors play an important role in their pathogenesis. Hence, common diseases should trigger the process of natural selection with subsequent population genetic response. However, empirical impact of natural selection on genetics of complex diseases is poorly understood. In this paper, I hypothesize that negative selection of diseased individuals leads to systemic genetic differences between common diseases that primarily occur before or during the reproductive years (early onset) and those that occur after the reproductive years (late onset). Methods. To test this hypothesis, a comprehensive literature survey of highly penetrant (80% or more) nonpleiotropic, nonsyndromic susceptibility genes (hereafter defined as Mendelian phenocopies...

Research paper thumbnail of A Recurrent Stop-Codon Mutation in Succinate Dehydrogenase Subunit B Gene in Normal Peripheral Blood and Childhood T-Cell Acute Leukemia

Research paper thumbnail of Krebs cycle enzymes as tumor suppressors

Drug Discovery Today: Disease Mechanisms, 2005

Positional cloning studies in rare human cancer families have uncovered that two well-known metab... more Positional cloning studies in rare human cancer families have uncovered that two well-known metabolic enzymes catalyzing successive steps in the Krebs cycle also function as classical tumor suppressor genes. Germline inactivating mutations in succinate dehydrogenase and fumarate hydratase genes cause hereditary paraganglioma and hereditary leiomyomatosis/renal cell cancer syndromes, respectively. Constitutive activation of previously unrecognized and distinct physiological pathways rather than disruption of the Krebs cycle could be the cause of neoplastic transformation in these disorders.

Research paper thumbnail of Screening: Correlation of genotype and phenotype in paraganglioma

Nature reviews. Endocrinology, 2009

Screening of patients with paraganglioma revealed a high prevalence of germ line mutations in gen... more Screening of patients with paraganglioma revealed a high prevalence of germ line mutations in genes encoding subunits of the succinate dehydrogenase complex, according to a new study. Should gene testing become a routine part of the clinical management of patients with paraganglioma?

Research paper thumbnail of Genetic Analysis in the Diagnosis of Familial Paragangliomas

Research paper thumbnail of Mitochondrial Tumor Suppressors

Mitochondria and Cancer, 2008

Research paper thumbnail of On the association of succinate dehydrogenase mutations with hereditary paraganglioma

Trends in Endocrinology & Metabolism, 2003

Hereditary paraganglioma (PGL) is characterized by the development of slow-growing, highly vascul... more Hereditary paraganglioma (PGL) is characterized by the development of slow-growing, highly vascularized tumors that can present either as hormonally silent head and neck tumors or as abdominal pheochromocytomas. PGL tumors are caused by germline inactivating heterozygous mutations in the SDHB, SDHC and SDHD genes, which encode three of the four subunits of succinate dehydrogenase (SDH; succinate:ubiquinone oxidoreductase; mitochondrial complex II). Here, potential mechanisms by which SDH mutations could lead to tumor development are discussed. Mechanisms that lead to variations in the prevalence, penetrance and expressivity of SDH subunit mutations remain to be clarified to improve the clinical management of PGL patients. Recently, germline mutations in the FH gene, the product of which (fumarate hydratase) catalyzes the conversion of fumarate to malate in the Krebs cycle, have been detected in a distinct hereditary tumor syndrome, which is characterized by uterine and skin leiomyomatosis and papillary renal cancer. Although the exact mechanisms of tumorigenesis in both disorders are unknown, SDH and FH could be involved in the control of cell proliferation under normal physiological conditions in the affected tissue types. Whereas SDH might be involved in hypoxic proliferation of paraganglia, FH might play an important role in the regulation of ammonium metabolism in smooth muscle cells.

Research paper thumbnail of Mitochondria: More than Mitochondrial DNA in Cancer

Research paper thumbnail of Genetics of familial paragangliomas

Otolaryngologic Clinics of North America, 2001

Genetic studies of hereditary paraganglioma tumors have increased the understanding of the biolog... more Genetic studies of hereditary paraganglioma tumors have increased the understanding of the biology of these fascinating tumors, with important clinical implications for diagnosis and treatment. This article focuses on the genetics of paraganglioma tumors, with limited reference to their general morphologic and clinical aspects. The paraganglioma tumor phenotype is defined. The genetic and physical mapping studies recently performed are summarized. These painstaking mapping studies eventually led to the discovery of the gene for hereditary paraganglioma type 1 (PGLZ). Finally, future directions stemming from the PGL gene discovery are described. PHENOTYPE Human genetics research explores how variations at the genetic level (i.e., cause) affect variations at the phenotypic level (i.e, effect) and relies heavily on the phenotype description, which is obtained by clinical and laboratory assessment. The phenotype of paraganglioma refers to the presence of tumors derived from paraganglionic tissue (i.e., the extra-adrenal chromaffin cell Paraganglioma tumors generally are classified on the basis of their anatomic location and common histology. Normal paraganglionic tissue is clustered near the cranial nerves and the arterial

Research paper thumbnail of Screening for familial paragangliomas

Oral Oncology, 2008

Paragangliomas of the head and neck are uncommon, slow-growing, multicentric and are usually beni... more Paragangliomas of the head and neck are uncommon, slow-growing, multicentric and are usually benign. Ever since familial paragangliomas were first described a genetic explanation for their existence has been sought. An international collaboration finally elucidated the SDHB, SDHC and SDHD genes for three paraganglioma syndromes (PGL 4, 3, 1). A familial origin should be suspected if other family members have paraganglioma, paragangliomas are multiple, the patient is young or the patient has a vagal paraganglioma. Once familial disease is suspected the best initial screening method is by genetic testing of the patient in question. If genetic testing detects PGL 1, 3 or 4 mutations then the patient's siblings and children should be tested. All genotypically positive patients should be followed periodically as soon as detected. Surveillance is best performed with periodic radionuclide imaging and by directed magnetic resonance imaging. The purpose of surveillance is early detection and consequently earlier treatment. Abundant evidence exists that the risk of complications from surgical intervention increases with increasing tumor size. If tumors are detected and eradicated before they become large, then younger patients can be spared the dysphagia, dysphonia, dysarthria and stroke that have plagued patients undergoing surgery for these tumors.

Research paper thumbnail of A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family

Neurogenetics, 2002

Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme ... more Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme mood swings. Genetic influences affect the disease susceptibility substantially, yet the underlying mechanisms are unknown. We previously described a pedigree in which all five individuals with BPAD and one individual with recurrent major depression were carriers of a reciprocal chromosomal translocation t(9;11)(p24;q23). Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1 ) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome. DIBD1 is predicted to encode a mannosyltransferase similar to Saccaromyces cerevisiae Alg9p of the protein N-glycosylation pathway. The in-born errors of protein N-glycosylation cause congenital disorders of glycosylation in humans. DIBD1 shows uniform expression in the tested subregions of the brain by Northern analysis. Sequence analysis revealed four intragenic single nucleotide polymorphisms. The valine residue at V289I was conserved in other eukaryotic species, whereas its frequency was approximately 65% in humans. We performed linkage and linkage disequilibrium analyses in two NIMH bipolar pedigree series using four tightly linked simple tandem repeat polymorphisms (STRPs) and the V289I. These analyses overall failed to support a role for DIBD1 in disease susceptibility. The most-significant finding was a lod score of 1.18 (P=0.0098), obtained by an intronic STRP D11S5025, in the subset of 22 multiplex pedigrees. In conclusion, we found that a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint co-segregating with BPAD in a family. However, its role in the disease susceptibility remains unconfirmed.

Research paper thumbnail of Additional file 6: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S5. C>U RNA editing events shared between NK cells and 293T/APOBEC3A, and NK cells, 293T... more Table S5. C>U RNA editing events shared between NK cells and 293T/APOBEC3A, and NK cells, 293T/APOBEC3A and 293T/APOBEC3G overexpression systems. (XLSX 14 kb)

Research paper thumbnail of Additional file 4: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S3. C>U RNA editing events after the third filter (stem-loop). These events are located ... more Table S3. C>U RNA editing events after the third filter (stem-loop). These events are located at the 3â ˛-end of loops in putative stem-loop structures within exons or UTRs. (XLSX 59 kb)

Research paper thumbnail of Additional file 3: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S2. C>U RNA editing events after the second filter (− 1 C or T). These events have C or ... more Table S2. C>U RNA editing events after the second filter (− 1 C or T). These events have C or T at − 1 nucleotide position. (XLSX 222 kb)

Research paper thumbnail of Additional file 2: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S1. C>U RNA editing events after the first filter (FDRâ

Research paper thumbnail of Additional file 1: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Figure S1-S12. Supplementary figures. (PPTX 1499 kb)

Research paper thumbnail of Additional file 10: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S9. Oligonucleotide primer sequences used for PCR amplification and Sanger sequencing. (XLS... more Table S9. Oligonucleotide primer sequences used for PCR amplification and Sanger sequencing. (XLSX 10 kb)

Research paper thumbnail of Additional file 9: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S8. Gene expression levels in normoxic and hypoxic NK cells. (XLSX 3002 kb)

Research paper thumbnail of Additional file 8: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S7. Evolutionary conservation analysis of all non-synonymous C>U RNA editing sites. (XLS... more Table S7. Evolutionary conservation analysis of all non-synonymous C>U RNA editing sites. (XLSX 18 kb)

Research paper thumbnail of Additional file 7: of Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells

Table S6. A>I RNA editing events in RADAR database that are induced by hypoxia in NK cells. (X... more Table S6. A>I RNA editing events in RADAR database that are induced by hypoxia in NK cells. (XLSX 11 kb)

Research paper thumbnail of Natural selection increases mutational robustness in complex diseases: Mendelian evidence from early versus late onset common diseases

Background. Natural selection operates on genetically influenced phenotypic variations that confe... more Background. Natural selection operates on genetically influenced phenotypic variations that confer differential survival or reproductive advantages. Common diseases are frequently associated with increased mortality and disability and complex heritable factors play an important role in their pathogenesis. Hence, common diseases should trigger the process of natural selection with subsequent population genetic response. However, empirical impact of natural selection on genetics of complex diseases is poorly understood. In this paper, I hypothesize that negative selection of diseased individuals leads to systemic genetic differences between common diseases that primarily occur before or during the reproductive years (early onset) and those that occur after the reproductive years (late onset). Methods. To test this hypothesis, a comprehensive literature survey of highly penetrant (80% or more) nonpleiotropic, nonsyndromic susceptibility genes (hereafter defined as Mendelian phenocopies...

Research paper thumbnail of A Recurrent Stop-Codon Mutation in Succinate Dehydrogenase Subunit B Gene in Normal Peripheral Blood and Childhood T-Cell Acute Leukemia

Research paper thumbnail of Krebs cycle enzymes as tumor suppressors

Drug Discovery Today: Disease Mechanisms, 2005

Positional cloning studies in rare human cancer families have uncovered that two well-known metab... more Positional cloning studies in rare human cancer families have uncovered that two well-known metabolic enzymes catalyzing successive steps in the Krebs cycle also function as classical tumor suppressor genes. Germline inactivating mutations in succinate dehydrogenase and fumarate hydratase genes cause hereditary paraganglioma and hereditary leiomyomatosis/renal cell cancer syndromes, respectively. Constitutive activation of previously unrecognized and distinct physiological pathways rather than disruption of the Krebs cycle could be the cause of neoplastic transformation in these disorders.

Research paper thumbnail of Screening: Correlation of genotype and phenotype in paraganglioma

Nature reviews. Endocrinology, 2009

Screening of patients with paraganglioma revealed a high prevalence of germ line mutations in gen... more Screening of patients with paraganglioma revealed a high prevalence of germ line mutations in genes encoding subunits of the succinate dehydrogenase complex, according to a new study. Should gene testing become a routine part of the clinical management of patients with paraganglioma?

Research paper thumbnail of Genetic Analysis in the Diagnosis of Familial Paragangliomas

Research paper thumbnail of Mitochondrial Tumor Suppressors

Mitochondria and Cancer, 2008

Research paper thumbnail of On the association of succinate dehydrogenase mutations with hereditary paraganglioma

Trends in Endocrinology & Metabolism, 2003

Hereditary paraganglioma (PGL) is characterized by the development of slow-growing, highly vascul... more Hereditary paraganglioma (PGL) is characterized by the development of slow-growing, highly vascularized tumors that can present either as hormonally silent head and neck tumors or as abdominal pheochromocytomas. PGL tumors are caused by germline inactivating heterozygous mutations in the SDHB, SDHC and SDHD genes, which encode three of the four subunits of succinate dehydrogenase (SDH; succinate:ubiquinone oxidoreductase; mitochondrial complex II). Here, potential mechanisms by which SDH mutations could lead to tumor development are discussed. Mechanisms that lead to variations in the prevalence, penetrance and expressivity of SDH subunit mutations remain to be clarified to improve the clinical management of PGL patients. Recently, germline mutations in the FH gene, the product of which (fumarate hydratase) catalyzes the conversion of fumarate to malate in the Krebs cycle, have been detected in a distinct hereditary tumor syndrome, which is characterized by uterine and skin leiomyomatosis and papillary renal cancer. Although the exact mechanisms of tumorigenesis in both disorders are unknown, SDH and FH could be involved in the control of cell proliferation under normal physiological conditions in the affected tissue types. Whereas SDH might be involved in hypoxic proliferation of paraganglia, FH might play an important role in the regulation of ammonium metabolism in smooth muscle cells.

Research paper thumbnail of Mitochondria: More than Mitochondrial DNA in Cancer

Research paper thumbnail of Genetics of familial paragangliomas

Otolaryngologic Clinics of North America, 2001

Genetic studies of hereditary paraganglioma tumors have increased the understanding of the biolog... more Genetic studies of hereditary paraganglioma tumors have increased the understanding of the biology of these fascinating tumors, with important clinical implications for diagnosis and treatment. This article focuses on the genetics of paraganglioma tumors, with limited reference to their general morphologic and clinical aspects. The paraganglioma tumor phenotype is defined. The genetic and physical mapping studies recently performed are summarized. These painstaking mapping studies eventually led to the discovery of the gene for hereditary paraganglioma type 1 (PGLZ). Finally, future directions stemming from the PGL gene discovery are described. PHENOTYPE Human genetics research explores how variations at the genetic level (i.e., cause) affect variations at the phenotypic level (i.e, effect) and relies heavily on the phenotype description, which is obtained by clinical and laboratory assessment. The phenotype of paraganglioma refers to the presence of tumors derived from paraganglionic tissue (i.e., the extra-adrenal chromaffin cell Paraganglioma tumors generally are classified on the basis of their anatomic location and common histology. Normal paraganglionic tissue is clustered near the cranial nerves and the arterial

Research paper thumbnail of Screening for familial paragangliomas

Oral Oncology, 2008

Paragangliomas of the head and neck are uncommon, slow-growing, multicentric and are usually beni... more Paragangliomas of the head and neck are uncommon, slow-growing, multicentric and are usually benign. Ever since familial paragangliomas were first described a genetic explanation for their existence has been sought. An international collaboration finally elucidated the SDHB, SDHC and SDHD genes for three paraganglioma syndromes (PGL 4, 3, 1). A familial origin should be suspected if other family members have paraganglioma, paragangliomas are multiple, the patient is young or the patient has a vagal paraganglioma. Once familial disease is suspected the best initial screening method is by genetic testing of the patient in question. If genetic testing detects PGL 1, 3 or 4 mutations then the patient's siblings and children should be tested. All genotypically positive patients should be followed periodically as soon as detected. Surveillance is best performed with periodic radionuclide imaging and by directed magnetic resonance imaging. The purpose of surveillance is early detection and consequently earlier treatment. Abundant evidence exists that the risk of complications from surgical intervention increases with increasing tumor size. If tumors are detected and eradicated before they become large, then younger patients can be spared the dysphagia, dysphonia, dysarthria and stroke that have plagued patients undergoing surgery for these tumors.

Research paper thumbnail of A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family

Neurogenetics, 2002

Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme ... more Bipolar affective disorder (BPAD) is a complex neuropsychiatric disease characterized by extreme mood swings. Genetic influences affect the disease susceptibility substantially, yet the underlying mechanisms are unknown. We previously described a pedigree in which all five individuals with BPAD and one individual with recurrent major depression were carriers of a reciprocal chromosomal translocation t(9;11)(p24;q23). Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1 ) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome. DIBD1 is predicted to encode a mannosyltransferase similar to Saccaromyces cerevisiae Alg9p of the protein N-glycosylation pathway. The in-born errors of protein N-glycosylation cause congenital disorders of glycosylation in humans. DIBD1 shows uniform expression in the tested subregions of the brain by Northern analysis. Sequence analysis revealed four intragenic single nucleotide polymorphisms. The valine residue at V289I was conserved in other eukaryotic species, whereas its frequency was approximately 65% in humans. We performed linkage and linkage disequilibrium analyses in two NIMH bipolar pedigree series using four tightly linked simple tandem repeat polymorphisms (STRPs) and the V289I. These analyses overall failed to support a role for DIBD1 in disease susceptibility. The most-significant finding was a lod score of 1.18 (P=0.0098), obtained by an intronic STRP D11S5025, in the subset of 22 multiplex pedigrees. In conclusion, we found that a mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint co-segregating with BPAD in a family. However, its role in the disease susceptibility remains unconfirmed.