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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
To explore the self-expressed desire for, envisioned reaction to, and basic understanding of presymptomatic Alzheimer disease (AD)-related genetic and biomarker tests.
The Alzheimer's Prevention ...Registry is an online community of people at least 18 years of age who are interested in AD prevention research for purely informational purposes or to be considered for possible research participation in future studies. Information about presymptomatic testing and an online multiple choice format survey were posted from November 1, 2012, through June 20, 2013, on the registry website.
Of 4036 respondents, 80.8% (3195/3952) wanted genetic testing if paid by insurance and 58.7% (2261/3851) if it would cost them at least $100. A total of 80.2% (3112/3879) wanted biomarker testing. If at high risk for AD, 90.5% (3478/3841) endorsed that they would "pursue a healthier lifestyle," but 11.6% (427/3706) endorsed "seriously consider suicide." The implication of a positive genetic test result was incorrectly understood by 13.1% (500/3812) and 32.6% (1255/3848) failed to view a positive biomarker test result as evidence of increased risk for or the presence of AD.
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.
Background
Women considering risk reduction surgery after a diagnosis of breast/ovarian cancer and/or inherited cancer gene mutation face difficult decisions. The safety of combined breast and ...gynecologic surgery has not been well studied; therefore, we evaluated the outcomes for patients who have undergone coordinated multispecialty surgery.
Methods
We conducted a retrospective review of patients undergoing simultaneous breast and gynecologic surgery for newly or previously diagnosed breast cancer and/or an inherited cancer gene mutation during the same anesthetic at a single institution from 1999 to 2013.
Results
Seventy-three patients with a mean age of 50 years (range 27–88) were identified. Most patients had newly diagnosed breast cancer or ductal carcinoma in situ (62 %) and 28 patients (38 %) had an identified BRCA mutation. Almost all gynecologic procedures were for risk reduction or benign gynecologic conditions (97 %). Mastectomy was performed in 39 patients (53 %), the majority of whom (79 %) underwent immediate reconstruction. The most common gynecologic procedure involved bilateral salpingo-oophorectomy, which was performed alone in 18 patients (25 %) and combined with hysterectomy in 40 patients (55 %). A total of 32 patients (44 %) developed postoperative complications, most of which were minor and did not require surgical intervention or hospitalization. Two of the 19 patients who underwent implant reconstruction (11 %; 3 % of the entire cohort) had major infectious complications requiring explantation.
Conclusion
Combined breast and gynecologic procedures for a breast cancer diagnosis and/or risk reduction in patients can be accomplished with acceptable morbidity. Concurrent operations, including reconstruction, can be offered to patients without negatively impacting their outcome.
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Screening for the Muir-Torre variant of Lynch Syndrome (LS) using Mismatch Repair (MMR) gene immunohistochemistry (IHC) on sebaceous neoplasms (SNs) is technically feasible. To date, research into ...the clinical utility of MMR IHC for this indication is limited. We conducted a retrospective chart review of 90 patients with MMR IHC completed on at least one SN from January 2005 to May 2010. SNs included were adenomas, epitheliomas, carcinomas and basal and squamous cell carcinomas with sebaceous differentiation. Of the 90 patients, 13 (14 %) had genetically confirmed or fulfilled clinical criteria for a diagnosis of MTS and 51 patients (57 %) presented with an abnormal MMR IHC result (loss of one or more MMR proteins) on at least one SN. Abnormal IHC had a sensitivity of 85 %, specificity of 48 %, positive predictive value (PPV) of 22 % and negative predictive value (NPV) of 95 % when evaluating for MTS. When personal or family history of colorectal cancer (≥2 family members with a history of colorectal cancer) was taken into consideration, ignoring IHC results, sensitivity was 92 %, specificity was 99 %, PPV was 92 % and NPV was 99 %. MMR IHC on SNs when used to screen for MTS has poor diagnostic utility. We recommend that MMR IHC not be performed routinely on SNs when the patient does not have either personal or family history of colorectal cancer.
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DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons ...in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Solving the mystery of booming sand dunes Vriend, Nathalie M.; Hunt, Melany L.; Clayton, Robert W. ...
Geophysical research letters,
28 August 2007, Volume:
34, Issue:
16
Journal Article
Peer reviewed
Open access
Desert booming can be heard after a natural slumping event or during a sand avalanche generated by humans sliding down the slip face of a large dune. The sound is remarkable because it is composed of ...one dominant audible frequency (70 to 105 Hz) plus several higher harmonics. This study challenges earlier reports that the dunes' frequency is a function of average grain size by demonstrating through extensive field measurements that the booming frequency results from a natural waveguide associated with the dune. The booming frequency is fixed by the depth of the surficial layer of dry loose sand that is sandwiched between two regions of higher compressional body wave velocity. This letter presents measurements of the booming frequencies, compressional wave velocities, depth of surficial layer, along with an analytical prediction of the frequency based on constructive interference of propagating waves generated by avalanching along the dune surface.
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To understand motivations, educational needs, and concerns of individuals contemplating whole-exome sequencing (WES) and determine what amount of genetic information might be obtained by sequencing a ...generally healthy cohort so as to more effectively counsel future patients.
From 2012 to 2014, 40 medically educated, generally healthy scientists at Mayo Clinic were invited to have WES conducted on a research basis; 26 agreed to be in a drawing from which 10 participants were selected. The study involved pre- and posttest genetic counseling and completion of 4 surveys related to the experience and outcomes. Whole-exome sequencing was conducted on DNA from blood from each person.
Most variants (76,305 per person; range, 74,505-77,387) were known benign allelic variants, variants in genes of unknown function, or variants of uncertain significance in genes of known function. The results of suspected pathogenic/pathogenic variants in Mendelian disorders and pharmacogenomic variants were disclosed. The mean number of suspected pathogenic/pathogenic variants was 2.2 per person (range, 1-4). Four pharmacogenomic genes were included for reporting; variants were found in 9 of 10 participants.
This study provides data that may be useful in establishing reality-based patient expectations, outlines specific points to cover during counseling, and increases confidence in the feasibility of providing adequate preparation and counseling for WES in generally healthy individuals.
1 Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of ...Health and Human Services, PO Box 2087, Fort Collins, CO 80522, USA
2 Alexion Antibody Technologies, San Diego, CA 92121, USA
Correspondence Ann R. Hunt arh4{at}cdc.gov
A humanized monoclonal antibody (mAb) has been developed and its potential to protect from or cure a Venezuelan equine encephalomyelitis virus (VEEV) infection was evaluated. The VEEV-neutralizing, protective murine mAb 3B4C-4 was humanized using combinatorial antibody libraries and phage-display technology. Humanized VEEV-binding Fabs were evaluated for virus-neutralizing capacity, then selected Fabs were converted to whole immunoglobulin (Ig) G1, and stable cell lines were generated. The humanized mAb Hy4-26C, designated Hy4 IgG, had virus-neutralizing capacity similar to that of 3B4C-4. Passive antibody protection studies with purified Hy4 IgG were performed in adult Swiss Webster mice. As little as 100 ng Hy4 IgG protected 90 % of mice challenged with 100 intraperitoneal (i.p.) mean morbidity (MD 50 ) doses of virulent VEEV (Trinidad donkey) 24 h after antibody transfer; also, 500 µg Hy4 IgG protected 80 % of mice inoculated with 100 intranasal MD 50 doses of VEEV. Moreover, 10 µg passive Hy4 IgG protected 70 % of mice from a VEEV challenge dose as great as 10 7 i.p. MD 50 . Hy4 IgG also protected mice from challenge with another epizootic VEEV variety, 1C (P676). Importantly, therapeutic administration of the humanized mAb to mice already infected with VEEV cured 90 % of mice treated with Hy4 IgG within 1 h of VEEV inoculation and 75 % of mice treated 24 h after virus infection.
Published online ahead of print on 7 June 2006 as DOI 10.1099/vir.0.81925-0.
The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are DQ487205DQ487208.
Supplementary tables are available in JGV Online.
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