The Experts below are selected from a list of 23325 Experts worldwide ranked by ideXlab platform
Laura Ottini - One of the best experts on this subject based on the ideXlab platform.
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the Cancer Genetics and pathology of male breast Cancer
Histopathology, 2016Co-Authors: Laura Ottini, Siddhartha Deb, Sunil R Lakhani, Stephen B FoxAbstract:Male breast Cancer (MBC) is an uncommon and poorly understood disease. Recent molecular studies have shown important differences from female breast Cancer which are likely to influence treatment strategies from the current female-based management towards a more tailored approach. Significantly more MBCs than female breast Cancers arise with an underlying germline Cancer predisposition, and display a vastly different penetrance compared with females. Furthermore, the genophenotypical association of basal-like Cancer with BRCA1 present in female breast Cancer is not observed in male breast Cancer. Differences in somatic changes between male and female breast Cancer have also been reported, with particular enrichment of PIK3CA mutations and a paucity of TP53 mutations. In general, chromosomal-based changes, in particular regions of gains, are seen more frequently in male than female breast Cancer and methylation is seen less frequently. Clinically, several molecular subtypes with prognostic relevance have been described, including chromosomal complex high and methylation high groups, and subgroups with profiling signatures pertaining to epithelial mesenchymal transition and hormonal therapy insensitivity. As with female breast Cancer, attention to male specific multicentre trials based on the individual characteristics are needed, together with establishment of reliable preclinical models to understand more clearly the pathogenesis of male breast Cancer and improve the general poor outcome of this disease.
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male breast Cancer Genetics epiGenetics and ethical aspects
Annals of Oncology, 2013Co-Authors: Piera Rizzolo, Valentina Silvestri, Stefania Tommasi, Rosamaria Pinto, Katia Danza, Mario Falchetti, Matteo Gulino, Paola Frati, Laura OttiniAbstract:Abstract Background and study design Male breast Cancer (MBC) is a rare disease compared with female BC and our current understanding regarding breast carcinogenesis in men has been largely extrapolated from the female counterpart. We focus on differences between the ethical issues related to male and female BC patients. A systematic literature search by using PubMed ( http://www.ncbi.nlm.nih.gov/pubmed/ ), was carried out to provide a synopsis of the current research in the field of MBC Genetics, epiGenetics and ethics. Original articles and reviews published up to September 2012 were selected by using the following search key words to query the PubMed website: ‘male breast Cancer’, ‘male breast Cancer and genetic susceptibility’, ‘male breast Cancer and epiGenetics’, ‘male breast Cancer and methylation’, ‘male breast Cancer and miRNA’, ‘male breast Cancer and ethics’. Results and conclusions As in women, three classes of breast Cancer genetic susceptibility (high, moderate, and low penetrance) are recognized in men. However, genes involved and their impact do not exactly overlap in female and male BC. Epigenetic alterations are currently scarcely investigated in MBC, however, the different methylation and miRNA expression profiles identified to date in female and male BCs suggest a potential role for epigenetic alterations as diagnostic biomarkers. Overall, much still needs to be learned about MBC and, because of its rarity, the main effort is to develop large consortia for moving forward in understanding MBC and improving the management of MBC patients on a perspective of gender medicine.
Alberto Bardelli - One of the best experts on this subject based on the ideXlab platform.
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liquid biopsy monitoring Cancer Genetics in the blood
Nature Reviews Clinical Oncology, 2013Co-Authors: Emily Crowley, Federica Di Nicolantonio, Fotios Loupakis, Alberto BardelliAbstract:As heterogeneity increasingly needs to be taken into account in the treatment of solid tumours, methods to detect genetic variation have come to the fore. One method that might have considerable clinical utility is the detection of variations in circulating-free DNA. This Review outlines the possibilities and challenges that this technique offers in terms of predictive and prognostic markers, as well as in the detection of therapy resistance. Cancer is associated with mutated genes, and analysis of tumour-linked genetic alterations is increasingly used for diagnostic, prognostic and treatment purposes. The genetic profile of solid tumours is currently obtained from surgical or biopsy specimens; however, the latter procedure cannot always be performed routinely owing to its invasive nature. Information acquired from a single biopsy provides a spatially and temporally limited snap-shot of a tumour and might fail to reflect its heterogeneity. Tumour cells release circulating free DNA (cfDNA) into the blood, but the majority of circulating DNA is often not of Cancerous origin, and detection of Cancer-associated alleles in the blood has long been impossible to achieve. Technological advances have overcome these restrictions, making it possible to identify both genetic and epigenetic aberrations. A liquid biopsy, or blood sample, can provide the genetic landscape of all Cancerous lesions (primary and metastases) as well as offering the opportunity to systematically track genomic evolution. This Review will explore how tumour-associated mutations detectable in the blood can be used in the clinic after diagnosis, including the assessment of prognosis, early detection of disease recurrence, and as surrogates for traditional biopsies with the purpose of predicting response to treatments and the development of acquired resistance.
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liquid biopsy monitoring Cancer Genetics in the blood
Nature Reviews Clinical Oncology, 2013Co-Authors: Emily Crowley, Federica Di Nicolantonio, Fotios Loupakis, Alberto BardelliAbstract:Cancer is associated with mutated genes, and analysis of tumour-linked genetic alterations is increasingly used for diagnostic, prognostic and treatment purposes. The genetic profile of solid tumours is currently obtained from surgical or biopsy specimens; however, the latter procedure cannot always be performed routinely owing to its invasive nature. Information acquired from a single biopsy provides a spatially and temporally limited snap-shot of a tumour and might fail to reflect its heterogeneity. Tumour cells release circulating free DNA (cfDNA) into the blood, but the majority of circulating DNA is often not of Cancerous origin, and detection of Cancer-associated alleles in the blood has long been impossible to achieve. Technological advances have overcome these restrictions, making it possible to identify both genetic and epigenetic aberrations. A liquid biopsy, or blood sample, can provide the genetic landscape of all Cancerous lesions (primary and metastases) as well as offering the opportunity to systematically track genomic evolution. This Review will explore how tumour-associated mutations detectable in the blood can be used in the clinic after diagnosis, including the assessment of prognosis, early detection of disease recurrence, and as surrogates for traditional biopsies with the purpose of predicting response to treatments and the development of acquired resistance.
Siddhartha Deb - One of the best experts on this subject based on the ideXlab platform.
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the Cancer Genetics and pathology of male breast Cancer
Histopathology, 2016Co-Authors: Laura Ottini, Siddhartha Deb, Sunil R Lakhani, Stephen B FoxAbstract:Male breast Cancer (MBC) is an uncommon and poorly understood disease. Recent molecular studies have shown important differences from female breast Cancer which are likely to influence treatment strategies from the current female-based management towards a more tailored approach. Significantly more MBCs than female breast Cancers arise with an underlying germline Cancer predisposition, and display a vastly different penetrance compared with females. Furthermore, the genophenotypical association of basal-like Cancer with BRCA1 present in female breast Cancer is not observed in male breast Cancer. Differences in somatic changes between male and female breast Cancer have also been reported, with particular enrichment of PIK3CA mutations and a paucity of TP53 mutations. In general, chromosomal-based changes, in particular regions of gains, are seen more frequently in male than female breast Cancer and methylation is seen less frequently. Clinically, several molecular subtypes with prognostic relevance have been described, including chromosomal complex high and methylation high groups, and subgroups with profiling signatures pertaining to epithelial mesenchymal transition and hormonal therapy insensitivity. As with female breast Cancer, attention to male specific multicentre trials based on the individual characteristics are needed, together with establishment of reliable preclinical models to understand more clearly the pathogenesis of male breast Cancer and improve the general poor outcome of this disease.
Christopher S Lathan - One of the best experts on this subject based on the ideXlab platform.
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abstract b32 utilization and outcomes of Cancer Genetics referrals at a community Cancer program
Cancer Epidemiology Biomarkers & Prevention, 2018Co-Authors: Ruth N Akindele, Huma Q Rana, Sarah R Cochrane, Ludmila Svoboda, Christopher S LathanAbstract:The majority of research on Cancer genetic counseling and testing has been conducted in academic medical centers and among predominantly Caucasian cohorts. Unfortunately, underserved and minority populations who have a disproportionate burden of Cancer have, historically, had limited access to and poor utilization of these services despite proven benefits of Cancer risk reduction in high-risk individuals. Based on a unique co-location model that addresses this disparity gap, the Dana-Farber Cancer Institute (DFCI)9s Cancer Care Equity Program (CCEP) added a Genetics arm to its Community Cancer Program (CCP), housed in a neighborhood Federally Qualified Community Health Center (FQHC) in 2013. The aim of this study was to determine clinic utilization rates, uptake, and outcomes of genetic evaluations as well as to describe the barriers to obtaining genetic testing among patients referred to the CCP. Methods: The intervention cohort consisted of patients referred to the CCP by their primary care providers (PCP) for Cancer Genetics counseling and testing between August 2013 and April 2017. A geneticist and a genetic counselor from DFCI9s Cancer Risk and Prevention Program provided risk assessment and counseling according to the National Comprehensive Cancer Network (NCCN) guidelines. Prospective data approved by the IRB were collected on a secured REDcap database that was designed for the CCEP. Information including attendance at clinic, patient demographics, personal and family history of Cancer or familial mutation, previous genetic testing for Cancer, recommendation for genetic testing, uptake, and results were extracted and analyzed descriptively (JMP Pro version 12, SAS Institute Inc., Cary, NC). Results: Seventy out of 118 patients referred by PCPs attended clinic, indicating a no-show rate of 41%. Of the 70, 62 (89%) consented to research. The mean age of the study population was 43 (SD±11.6) years and 87% were women. More than half of the participants (57%) were Blacks/African Americans (Non-Hispanic-31% and Hispanic-26%), 32% were Whites (Non-Hispanic-13% and Hispanic-19%), and 8% were other races. Interpreter services, mainly Spanish, were provided for 32% of participants. The majority (76%) had Medicaid insurance, 8% had Medicare,13% had private insurance, and 3% had health safety net/free care. While not mutually exclusive, 66% of participants reported a family history of breast Cancer, 32% ovarian Cancer, 23% colorectal Cancer, and 23% other Cancers. There were two (3%) participants with a personal history of Cancer, two (3%) with a presence of familial mutation among family members (BRCA 1/2), and two (3%) with prior genetic testing. Of the two who had prior testing, one had a familial mutation (APC). Overall, 43 (69%) participants were recommended for genetic testing. The most frequent reason for non-recommendation was that there was a better testing candidate in the family (53%). Another 21% were asked to clarify their family history before completing Cancer risk assessment. Of the 43 who were recommended for testing, 32(74%) completed testing with nearly all (91%) testing for multigene panels. Lack of insurance coverage was the most frequent (73%) reason for not undergoing a test. Among those who completed testing, a pathogenic mutation (MUTYH) was identified in one participant (3%), while 13 (39%) had variants of unknown significance (VUS) and 18 (59%) had no mutations identified. Conclusions: Our findings highlight the need for increased knowledge of family history and utilization of Cancer genetic services among underserved and minority populations. Additionally, efforts should be made to improve insurance coverage for genetic testing in high-risk underserved individuals. Further research on the clinical significance of variants of uncertain significance identified in ethnic minority populations is also advised. Citation Format: Ruth N. Akindele, Huma Q. Rana, Sarah R. Cochrane, Ludmila A. Svoboda, Christopher S. Lathan. Utilization and outcomes of Cancer Genetics referrals at a community Cancer program [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B32.
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a comparison of Cancer risk assessment and testing outcomes in patients from underserved vs tertiary care settings
Journal of Community Genetics, 2018Co-Authors: Huma Q Rana, Judy Garber, Ruth N Akindele, Sarah R Cochrane, Ludmila Svoboda, Elaine Hiller, Callie Nibecker, Angel M Cronin, Christopher S LathanAbstract:In Cancer Genetics, technological advances (next generation sequencing) and the expansion of genetic test options have resulted in lowered costs and increased access to genetic testing. Despite this, the majority of patients utilizing Cancer Genetics services lack diversity of gender, ethnicity, and socioeconomic status. Through retrospective chart review, we compared outcomes of Cancer Genetics consultations at a tertiary Cancer center and a Federally Qualified Health Center (FQHC) (58 tertiary and 23 FQHC patients) from 2013 to 2015. The two groups differed in race, ethnicity, use of translator services, and type of insurance coverage. There were also significant differences in completeness of family history information, with more missing information about relatives in the FQHC group. In spite of these differences, genetic testing rates among those offered testing were comparable across the two groups with 74% of tertiary patients and 60% of FQHC patients completing testing. Implementation of community-based Cancer Genetics outreach clinics represents an opportunity to improve access to genetic counseling services, but more research is needed to develop effective counseling models for diverse patient populations.
Ethan M Lange - One of the best experts on this subject based on the ideXlab platform.
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hoxb13 is a susceptibility gene for prostate Cancer results from the international consortium for prostate Cancer Genetics icpcg
Human Genetics, 2013Co-Authors: Jianfeng Xu, Ethan M Lange, Lingyi Lu, Siqun L Zheng, Zhong Wang, Stephen N Thibodeau, Lisa A Cannonalbright, Craig C Teerlink, Nicola J CampAbstract:Prostate Cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate Cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate Cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate Cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate Cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate Cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 × 10−8 [odds ratio 4.42 (95 % confidence interval 2.56–7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 × 10−6). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of Cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate Cancer families, predominantly of European descent, and confirm its association with prostate Cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous Cancer. Electronic supplementary material The online version of this article (doi:10.1007/s00439-012-1229-4) contains supplementary material, which is available to authorized users.
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early onset prostate Cancer has a significant genetic component
The Prostate, 2012Co-Authors: Ethan M Lange, Claudia A Salinas, Lindsey A Ho, Kimberly A Zuhlke, Yunfei Wang, Yurong Lu, Kathleen A. CooneyAbstract:BACKGROUND. Prostate Cancer (PCa) affects more than 190,000 men each year with � 10% of men diagnosed at � 55 years, that is, early onset (EO) PCa. Based on historical findings for other Cancers, EO PCa likely reflects a stronger underlying genetic etiology. METHODS. We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina’s iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS).
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genome wide linkage scan for prostate Cancer susceptibility from the university of michigan prostate Cancer Genetics project suggestive evidence for linkage at 16q23
The Prostate, 2009Co-Authors: Ethan M Lange, Kimberly A Zuhlke, Yunfei Wang, Jennifer L Beebedimmer, Anna M Ray, Jaclyn Ellis, Sarah Walters, Kathleen A. CooneyAbstract:BACKGROUND Prostate Cancer linkage studies have been used to localize rare and presumably highly penetrant Cancer susceptibility genes. Underlying genetic heterogeneity, as well as the high sporadic background of the disease, has resulted in many signals that are often not reproducible between research studies. METHODS We conducted a SNP-based genome wide linkage scan on 131 Caucasian prostate Cancer families participating in the University of Michigan Prostate Cancer Genetics Project (PCGP). RESULTS The strongest evidence for linkage was detected at 16q23 (LOD = 2.70 at rs1079635). Prostate Cancer linkage to the same region of 16q23 has been observed by others and the region contains several strong candidate genes including the known prostate Cancer tumor suppressor genes ATBF1 and WWOX. This linkage signal was not detected in our prior linkage study on 175 PCGP families, illustrating the genetic heterogeneity underlying prostate Cancer susceptibility. CONCLUSIONS Further linkage studies in combination with tumor analyses from linked families are in progress to identify the putative hereditary prostate Cancer gene at 16q23. Prostate 69:385–391, 2009. © 2008 Wiley-Liss, Inc.
