Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the FGFR2 locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (in vitro FGFR2 IC50≈350 nM) was noted in a patient with an FGFR2-TACC3 fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (in vitro, FGFR2 IC50≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in ERRFI1, a direct negative regulator of EGFR activation. Rapid and robust disease regression was noted in this ERRFI1 inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. FGFR2 fusions and ERRFI mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.

Updated from their original publication in 2004, these cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of counseling at-risk individuals through genetic cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Familial Cancer Risk Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Essential components include the intake, cancer risk assessment, genetic testing for an inherited cancer syndrome, informed consent, disclosure of genetic test results, and psychosocial assessment. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

These cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Cancer Genetic Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Key components include the intake (medical and family histories), psychosocial assessment (assessment of risk perception), cancer risk assessment (determination and communication of risk), molecular testing for hereditary cancer syndromes (regulations, informed consent, and counseling process), and follow-up considerations. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

Objective To explore, among online visitors to an Alzheimer’s disease (AD) website, the self-expressed desire for, envisioned reaction to, and basic understanding of presymptomatic AD-related genetic and biomarker tests. Patients and Methods Information about presymptomatic testing, and an online multiple choice format survey were posted from November 1, 2012 through June 20, 2013 on the AD Prevention Registry website (www.endALZnow.org). Results Of 4036 respondents, 80.8% wanted genetic testing if paid by insurance; 58.7% if it would cost them at least $100. 80.2% wanted biomarker testing. If found to be at high risk for AD, 90.5% endorsed that they would “pursue a healthier lifestyle,” but 11.6% endorsed “seriously consider suicide.” The implication of a positive genetic test was incorrectly understood by 13.1%, and 32.6% failed to view a positive biomarker test as evidence of either increased risk for or the presence of AD. Conclusion Despite efforts to increase public awareness of AD, our survey results suggest that greater education of the public is needed. Interested patients should probably undergo psychological screening to identify those at high risk of adverse psychological outcomes, and disclosure of presymptomatic test results should be anchored to tangible constructive action plans such as healthy lifestyle changes, long term care planning, and when available and appropriate, participation in research trials.

Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian cancer. Detection before the disease has spread beyond the ovary would significantly improve the survival from ovarian cancer, which is currently only 30% over 5 years, despite extensive efforts to improve the survival. This study describes initial investigation of the use of optical technologies to improve the outcome for this disease by detecting cancers at an earlier and more treatable stage. Women undergoing oophorectomy were recruited for this study. Ovaries were harvested for fluorescence spectroscopy, confocal microscopy, and optical coherence tomography. Fluorescence spectroscopy showed large diagnostic differences between normal and abnormal tissue at 270 and 340 nm excitation. Optical coherence tomography was able to image up to 2mm deep into the ovary with particular patterns of backscattered intensity observed in normal versus abnormal tissue. Fluorescence confocal microscopy was able to visualize sub-cellular structures of the surface epithelium and underlying cell layers.Optical imaging and/or spectroscopy has the potential to improve the diagnostic capability in the ovary, but extended systematic investigations are needed to identify the unique signatures of disease. The combination of optical technologies supported by modern molecular biology may lead to an instrument that can accurately detect early carcinogenesis.Key word: Ovarian cancer imaging. IntroductionOvarian cancer goes undetected in both developed and developing countries because adequate technology does not exist to detect preinvasive or early stage disease. There are approximately 25,600 new cases of ovarian cancer in the United States per year, and an estimated 16,000 deaths from ovarian cancer in 2004 (1, 2). Although ovarian cancer accounts for only 4% of all new cancer cases, it is the fifth leading cause of cancer-related mortality in women, and the leading cause of death from gynecologic malignancies (3). High prevalence of late-stage disease and the poor prognosis associated with these later stages are the major factors that give ovarian cancer patients such a dismal prognosis. Women with disease localized to the ovary have a 5-year survival of 80-90%, while women with Stage III disease have a 5-year survival of 30% or less. With our current screening and diagnostic abilities, 70% of women will continue to be diagnosed with FIGO Stage III or IV disease (widespread intra-abdominal disease) and the majority of them will die of their disease (3). The conservative cost of treatment for ovarian cancer is estimated at least $15 billion dollars/year (4-6), due primarily to the late stage of diagnosis, the high morbidity associated with treatment, and the high rate of recurrence.Large cancers are easily detected at the time of surgery. However, occult cancers, which are only seen when ovaries are carefully sectioned and cannot be detected by visual assessment at the time of surg...