The NCI/NIH Cancer Moonshot BioBank (CMB) and the Maine Cancer Genetics/Genomics Education Core (ME-CGEC) Collaborate to Improve Cancer Care in Maine

Goal: To better understand drug resistance and sensitivity in patients with late stage (Stage III & IV) cancers that are receiving standard of care molecularly targeted therapies through next generation sequencing (NGS) of biopsy and blood samples collected longitudinally (diagnosis-- treatment--progression).https://knowledgeconnection.mainehealth.org/lambrew-retreat-2021/1053/thumbnail.jp

Development of fragment-specific osteopontin antibodies and ELISA for quantification in human metastatic breast cancer

Background: Osteopontin (OPN) is associated with human cancers, and circulating blood OPN may have diagnostic or prognostic value in clinical oncology. Methods: To evaluate OPN as a cancer biomarker, we generated and characterized five novel mouse monoclonal antibodies against the human full-length OPN (fl-OPN). Epitopes recognized by four antibodies (2C5, 2F10, 2H9, and 2E11) map to N-terminal OPN (aa1-166); one (1F11) maps to C-terminal OPN (aa167-314). These antibodies recognize recombinant and native OPN by ELISA and immunoblot, cross reacting with human and mouse OPN. Two of these novel antibodies ( 2F10 and 1F11) were used to develop a quantitative enzyme linked immunosorbent assay ( ELISA) for fl-OPN. Results: In comparison with commercially available ELISAs, our assay had high accuracy in measuring fl-OPN standards, and high sensitivity. Specifically, our ELISA has a linear dose response between 0.078 ng/ml- 10 ng/ml, with a sensitivity of 13.9 pg/ml. We utilized this assay to quantify fl-OPN in the plasma of healthy volunteers in comparison with patients with metastatic breast cancer. The average circulating plasma fl-OPN in healthy volunteers was 1.2 ng/ml, compared to 4.76 ng/ml in patients with metastatic breast cancer (p = 0.0042). Although the increase in fl-OPN in cancer patients is consistent with previous studies, the measured quantity varied greatly between all existing fl-OPN ELISAs. Conclusion: Because OPN is a complex molecule with diversity from alternative splicing, post-translational modification, extracellular proteolytic modification, and participation in protein complexes, we suggest that further understanding of specific isoform recognition of multiple OPN species is essential for future studies of OPN biomarker utility

Physician-patient communication about genomic tumor testing: perceptions of oncology providers

Background: • Genomic tumor testing (GTT) is a new technology and a cornerstone of the “precision medicine” movement in cancer care. • GTT uses next-generation genome sequencing technology to identify somatic variants in tumor cells. • By identifying somatic variants that predict responses to cancer therapies, GTT can help tailor therapy to individual patients, making them more effective. • However, due to the fact that GTT also detects many variants of uncertain significance, its clinical value is currently unproven. • When using GTT, physicians counsel patients about both its benefits and its limitations, but the ideal goals and content of these physician-patient discussions have not been clearly defined

Community oncology clinicians’ knowledge, beliefs, and attitudes regarding genomic tumor testing

Introduction: Genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise. However, little is known about clinicians’ knowledge, beliefs, and attitudes regarding GTT, particularly in community oncology settings

Community oncologists\u27 perceptions and utilization of large-panel genomic tumor testing.

PURPOSE: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists\u27 perceptions and use of GTT, but little is known about community oncologists\u27 perceptions of GTT and how perceptions relate to clinicians\u27 intentions to use GTT. METHODS: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them. RESULTS: There was substantial variability in clinicians\u27 perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients\u27 ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians\u27 future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT. CONCLUSIONS: Community oncologists\u27 perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice

DNA fragments of altered electrophoretic mobility in leukemia samples can arise from double-strand DNA breaks at nuclease hypersensitive sites of active genes

Chromosome translocations that disrupt or alter gene function have been implicated in the pathogenesis of a variety of malignancies. Therefore, identification of a translocation breakpoint has become a more important means by which to identify genes involved in cellular transformation. A common site of translocation in myeloid and lymphoid malignancies involves 11q23. One human protooncogene, ETS1, has been localized to this chromosomal segment, and several tumors with 11q23 translocations have been shown to have altered ETS1 DNA migration after restriction enzyme digestion. Two laboratories, however, have recently localized the 11q23 breakpoint region to a small region of DNA telomeric of the CD3 loci, a region at considerable distance from the ETS1 gene locus. Therefore, it is difficult to reconcile the studies that suggest altered migration of fragments associated with ETS1 and lack of a localization of the breakpoint to a region near the ETS1 gene. Recently, in our studies to characterize the promoter/enhancer region of the ETS1 protooncogene, we had the opportunity to analyze DNA from 18 patients with acute leukemia involving chromosome 11q23 aberrations. We were unable to demonstrate rearrangement of the ETS1 gene in this group, thus confirming that the 11q23 breakpoint does not involve ETS1 protooncogene. In one patient, however, a DNA break in the region of the ETS1 promoter was detected reproducibly. This DNA break was mapped to the major DNaseI hypersensitive site in the ETS1 promoter. Mapping from both sides of the break demonstrated that the break must have occurred during processing of the leukemic cells for DNA analysis. Therefore, artifactual DNA breaks can occur at nuclease-hypersensitive sites of active genes. These data suggest that previous reports of chromosomal translocations involving the ETS1 protooncogene may have resulted from DNA breaks at nuclease hypersensitive sites. This mechanism may account for sporadic case reports of altered restriction enzyme fragment migration involving genes that are not ultimately shown to be associated with the chromosome translocation being examined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30693/1/0000338.pd

Risk perception and concern among brothers of men with prostate carcinoma

BACKGROUND It is important for clinicians, researchers, and others who shape public health policy to understand the demographic correlates and psychologic factors that drive health behaviors, such as screening for early detection of cancer, particularly among individuals at high risk for developing the disease. METHODS One-hundred eleven men whose brothers were diagnosed with prostate carcinoma completed a computer-assisted telephone interview aimed to assess their perception of absolute risk and concern about developing prostate carcinoma over the next 10 years and across their lifetime. Comparisons were made between selected demographic, behavioral, family pedigree characteristics, and measures of perceived risk and concern. RESULTS The majority of men perceived their personal risk of developing prostate carcinoma to be ≥ 50%. Men who at the time of the interview were younger than their affected brother were significantly more concerned about prostate carcinoma and perceived their risk to be higher than men who were older than their brother. Estimates of personal risk and concern were also uniformly higher among men with more than one first-degree relative affected with prostate carcinoma compared to men with only one affected first-degree relative. Risk perception and concern about an impending prostate carcinoma diagnosis were associated with the use of supplements marketed for prostate health. CONCLUSIONS The findings indicated that birth order in relation to a brother diagnosed with prostate carcinoma is significantly associated with risk perception and concern in unaffected family members. These results highlight the need for further study of the familial dynamics and characteristics that drive health behaviors and stress importance of public health education to inform men of personal risk assessment as well as the risks and benefits of screening. These studies ultimately can contribute to the success of strategies for the primary prevention and early detection of cancer. Cancer 2004;100:1537–44. © 2004 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34386/1/20121_ftp.pd

Men's values-based factors on prostate cancer risk genetic testing: A telephone survey

BACKGROUND: While a definitive genetic test for Hereditary Prostate Cancer (HPC) is not yet available, future HPC risk testing may become available. Past survey data have shown high interest in HPC testing, but without an in-depth analysis of its underlying rationale to those considering it. METHODS: Telephone computer-assisted interviews of 400 men were conducted in a large metropolitan East-coast city, with subsequent development of psychometric scales and their correlation with intention to receive testing. RESULTS: Approximately 82% of men interviewed expressed that they "probably" or "definitely" would get genetic testing for prostate cancer risk if offered now. Factor analysis revealed four distinct, meaningful factors for intention to receive genetic testing for prostate cancer risk. These factors reflected attitudes toward testing and were labeled "motivation to get testing," "consequences and actions after knowing the test result," "psychological distress," and "beliefs of favorable outcomes if tested" (α = 0.89, 0.73, 0.73, and 0.60, respectively). These factors accounted for 70% of the total variability. The domains of motivation (directly), consequences (inversely), distress (inversely), and positive expectations (directly) all correlated with intention to receive genetic testing (p < 0.001). CONCLUSIONS: Men have strong attitudes favoring genetic testing for prostate cancer risk. The factors most associated with testing intention include those noted in past cancer genetics studies, and also highlights the relevance in considering one's motivation and perception of positive outcomes in genetic decision-making

Long-Term Adaptation Among Adolescent and Young Adult Children to Familial Cancer Risk

BACKGROUND: It is important to examine adolescent and young adult (AYA) children\u27s long-term psychosocial and behavioral adaptation to disclosure of maternal BRCA-positive carrier status (BRCA+) to inform approaches for familial cancer risk communication, education, and counseling. METHODS: Mothers underwent BRCA genetic testing 1 to 5 years earlier. Group differences in AYAs\u27 self-reported outcomes were analyzed by maternal health and carrier status, and child age and sex. RESULTS: A total of N = 272 AYAs were enrolled: 76.1% of their mothers were breast or ovarian cancer survivors and 17.3% were BRCA+. AYAs\u27 cancer risk behavior (tobacco and alcohol use, physical activity) and psychologic distress levels did not vary by maternal status. In bivariate analyses, AYAs of cancer-surviving mothers believed themselves to be at greater risk for, and were more knowledgeable about, cancer than AYAs of mothers without cancer. AYAs of BRCA+ mothers were more concerned about cancer, held stronger beliefs about genetic risk, and placed a higher value on learning about genetics. In adjusted models, maternal cancer history (not BRCA+) remained associated with AYAs\u27 greater perceptions of cancer risk (P = .002), and knowledge about cancer (P = .03) and its causes (P = .002). CONCLUSIONS: Disclosing maternal BRCA+ status did not influence children\u27s lifestyle behavior or adversely affect quality of life long term. AYAs of BRCA+ mothers were more aware of and interested in genetic risk information. Such families may benefit from support to promote open communication about genetic testing choices