Biospecimen Resource Research Articles

1. NCI Cancer specimen biorepositories

High quality biospecimens with appropriate clinical annotation are critical in the era of personalized medicine. It is now widely recognized that biospecimen resources need to be developed and operated under established scientific, technical, business, and ethical/legal standards. To date such standards have not been widely practiced, resulting in variable biospecimen quality that may compromise research efforts. The National Cancer Institute (NCI) Biorepositories and Biospecimen Research Branch (BBRB) was established in 2005 to coordinate NCI’s biospecimen resource activities, and address those issues that affect access to the high quality specimens and data necessary for its research enterprises, as well as the broader translational research field. BBRB developed NCI’s Best Practices for Biospecimen Resources after consultation with a broad array of experts. A Biospecimen Research Network was established to fund research to develop additional evidence-based practices. Projects are in progress to study preanalytical variables that may affect biospecimen quality and suitability for proteomic and genomic analyses. BBRB is also engaged in the NIH Genotype Tissue Expression (GTEx) Project, for which we have implemented a complex biospecimen collection and processing infrastructure that will result in analyses of genetic variation and gene expression across many tissues, to aid in the interpretation of genome-wide association study hits, to help prioritize therapeutic targets, and to further our understanding of genome regulation.

Abstract 2373: The LCBRN: a biospecimen resource for lung cancer biomarker and discovery science.

Abstract The Lung Cancer Biospecimen Resource Network (LCBRN) is an open access biorepository that obtains specimens from lung cancer patients (tissue, blood, urine, bronchial lavage fluid and saliva) and makes them available to biomedical researchers. Specimen collection is supported at 3 collection sites (Medical University of South Carolina, The University of Virginia, and Washington University at St. Louis) in compliance with uniform standard operating procedures. The specimens are annotated with clinical, radiologic and pathologic data. Histologic and molecular quality control procedures are in place for tissue samples. Lung cancer and non-neoplastic lung tissue aliquots are processed into DNA, RNA and protein fractions, which are also available. Fluid biosamples are available from subjects prior to, and after surgery to remove the cancer. A cohort of subjects are followed for recurrence with serial biofluid sampling. Specimens are currently available from over 300 research subjects. The application form for biospecimens and additional information is available at http://LCBRN.org. Citation Format: Christopher A. Moskaluk. The LCBRN: a biospecimen resource for lung cancer biomarker and discovery science. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2373. doi:10.1158/1538-7445.AM2013-2373

Abstract 3553: Elevated expression of mismatch repair enzyme MLH1 is associated with prolonged overall survival in resected pancreatic cancer treated with adjuvant chemoradiation, a biomarker analysis of RTOG 9704.

Abstract Introduction RTOG 9704 was a randomized phase III trial comparing two different adjuvant protocols in patients with resected pancreatic adenocarcinoma. All patients received concurrent 5FU-radiation (RT) therapy, in addition the control arm received 5FU prior to- and following RT, whereas the experimental arm received gemcitabine. MLH1 loss is associated with treatment resistance and genetic instability in the laboratory. It is hypothesized that tumors with higher levels of MLH1 expression would have a better prognosis. Methods A Tissue microarray prepared from paraffin blocks removed at time of operation was examined for MLH1 expression using fluorescence immunohistochemistry and analyzed using automated quantitative analysis software (AQUA) from HistoRx. For the purposes of part of the analysis MLH1 levels were dichotomized above and below the median expression value. Clinical endpoints were disease-free and overall-survival. Statistical techniques included the chi-square, Fisher's exact test and the Kaplan-Meier method. A p-value of <0.01 was considered significant to allow for multiple comparisons. Results Of the 451 eligible patients enrolled on the trial, immunohistochemistry staining was successfully performed for 117 patients for MLH1 (60 and 57 from the 2 arms). Characteristics from those with tissue were similar to the trial population as a whole. At the time of analysis 84% of the participants had died, with a median survival of 17 months (min-max: 14 to 21 months). Elevated MLH1 levels in tumor nuclei were correlated with longer disease-free and overall survival in both arms of the trial, both individually and combined. Two year overall survival was 16% in those with low MLH1 levels and 53% for those with high levels, p<0.0001 (both arms combined). This association remained true on multivariate analysis allowing for nodal status (HR=0.41, p<0.0001). Conclusions The expression of MLH1 correlates with long-term survival in resected pancreatic cancer treated with post-operative chemoradiation. It is suggested that, following validation, MLH1 be used as stratification markers in future clinical trials of DNA damaging agents in pancreatic cancer. This project was supported by RTOG grants U10 CA21661, CCOP grant U10 CA37422, and RTOG Biospecimen Resource grant U24 CA114734 from the National Cancer Institute (NCI). Citation Format: Yaacov Richard Lawrence, Jennifer Moughan, Anthony Magliocco, Alexander Klimowicz, William F. Regine, Rex B. Mowat, Thomas A. DiPetrillo, William Small, Kathryn Winter, Chandan Guha, Christopher Crane, Adam P. Dicker. Elevated expression of mismatch repair enzyme MLH1 is associated with prolonged overall survival in resected pancreatic cancer treated with adjuvant chemoradiation, a biomarker analysis of RTOG 9704. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3553. doi:10.1158/1538-7445.AM2013-3553

Meeting research needs with postmortem biospecimen donation: summary of recommendations for postmortem recovery of normal human biospecimens for research.

Normal human tissues, bodily fluids, and other biospecimens of known quality are essential for research to understand the development of cancer and other diseases and to develop new diagnostics and therapies. However, obtaining normal biospecimens appropriate for contemporary large-scale molecular and genomic research is one of the most challenging biospecimen acquisition problems for scientists and biospecimen resources that support research. Recognizing this challenge, the U.S. National Cancer Institute recently convened a series of workshops and meetings focused on the acquisition of normal tissues for research and produced an extensive document, Recommendations for Postmortem Recovery of Normal Human Biospecimens for Research. This article summarizes these recommendations, addressing key ethical, operational, and scientific elements for collecting normal reference biospecimens from postmortem donors in the U.S. Awareness of these recommendations can foster more effective collaborations and mitigate potential logistical challenges, while promoting postmortem biospecimen donation options for families and increasing the availability of high quality normal biospecimens for research. The recommendations have been put into practice in the collection of normal human biospecimens for the NIH Genotype-Tissue Expression Program (GTEx), a pilot study of human gene expression and regulation in multiple tissues which will provide valuable insights into the mechanisms of gene regulation and, in the future, its disease-related perturbations (http://commonfund.nih.gov/GTEx/).

Quality assessment of saliva bank samples.

Biospecimens, such as urine, blood, saliva, tissue, cells, DNA, RNA, and protein, are biological material to be stored in a biorepository. They constitute critical resources of molecular data for basic and translational research integrated with diagnostic, therapeutics, and prevention of human diseases. The reliability of the molecular data is dependent on the quality and the consistency of the biospecimen being analyzed. The potential of human saliva as a valuable diagnostic fluid for oral and systemic conditions is being increasingly recognized. The aim of this study is to determine the molecular quality of unstimulated whole saliva (UWS) samples stored over a period of 1 to 5 years. UWS samples collected between 2006 and 2010 (20/year) and stored at -80°C were assessed for molecular integrity. The study was approved by the institutional review board of the Indiana University Purdue University at Indianapolis. Qualitative and quantitative measurements of salivary proteins were determined by gel electrophoresis and spectrophotometry. The salivary nucleic acid content was determined by the Nanodrop method and genetic analysis. The nature of the cellular sediment in the UWS was determined by amplification of specific gene. No significant differences were observed in the amount of proteins, nucleic acid, or in the number of viable cells in the UWS samples stored for 1 to 5 years. Archived UWS samples could function as excellent biospecimen resources for measurement of protein, DNA, and RNA analytes, and act as an efficient source for human epithelial cells.

Abstract 5520: How widely shared are institutional human biospecimen resources: a comparison of an institutional-level response versus a PI-level response

Abstract Introduction/Background: The MinorityBiospecimen/Biobanking-Geographic Management Program (BMaP) is supported by the CRCHD of the NCI, to create state-of-the-art networks/centers dedicated to ensuring the adequate and continuous supply of high-quality human biospecimens from multi-ethnic communities for cancer research. A regional hub infrastructure was established with specific cores: administration, training, bioinformatics, biospecimen/biobanking, community translation, emerging technologies, and ethical-legal-policy issues. Two survey tools were employed to identify regional resources, including biospecimen collection and sharing practices: the NCI-developed Readiness Assessment Tool (RAT) and a regional-specific online Comprehensive Needs Assessment (CNA). These tools demonstrated the absence of central institutional biospecimen records at our partner institutions. This observation prompted a qualitativepilot study to assess the attitudes and barriers of researchers in the region to sharing biospecimens and participating in a virtual national biorepository. Methods: An online survey tool was developed to assess general receptiveness toward biobanks, presumed usefulness of biobanks, and perceived attitudes and barriers in recruiting patients for biobanks. We identified investigators working directly and indirectly, or planning to work with human biospecimens at Region 4 institutions (AZ, CO, NM, OK, TX). Participants’ email addresses were obtained from a publically available NIH-funded database (NIH RePorter), and an email inviting them to participate was sent along with the secure link to access the survey online. Participants were followed up with reminder emails at 2 and 4 weeks to complete the survey. Results: The RAT and the CNA identified several challenges regarding biospecimen collections: few of the Region 4 participants utilize biospecimens routinely in their research; there are no central institutional biospecimen records, so resource listings are all ad hoc; lack of desire and trust by some ethnic groups to contribute to biospecimen research; biospecimens collection between institutions may have problems due to lack of trust between target populations; and certain collaborating institutions and some repositories fail to cooperate due to competition, territorial issues, and lack of communication. Results from the pilot study will help generate recommendations and hypotheses regarding biospecmien sharing and participation in a virtual national biorepository among the 485 Region 4 researchers. Identifying the barriers to sharing biospecimens and participating in a national virtual biorepository will in turn result in strengthening collaborative opportunities among researchers in the region through the sharing of biospecimen data collections. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5520. doi:1538-7445.AM2012-5520

Fluorescence In Situ Hybridization to Visualize Genetic Abnormalities in Interphase Cells of Acinar Cell Carcinoma, Ductal Adenocarcinoma, and Islet Cell Carcinoma of the Pancreas

To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas. Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS. These FISH probes were used with control probes to distinguish among various kinds of chromosome abnormalities of number and structure. FISH abnormalities were observed in 12 (80%) of 15 patients with pancreatic cancer: 5 of 5 patients with acinar cell carcinoma, 5 of 5 patients with ductal adenocarcinoma, and 2 (40%) of 5 patients with islet cell carcinoma. All 3 specimens of pancreatic tissue without neoplasia had normal FISH results. Gains of CTNNB1 due to trisomy 3 occurred in each tumor with acinar cell carcinoma but in none of the other tumors in this study. FISH abnormalities of all other cancer genes studied were observed in all forms of pancreatic tumors in this investigation. FISH abnormalities of CTNNB1 due to trisomy 3 were observed only in acinar cell carcinoma. FISH abnormalities of genes implicated in familial cancer, tumor progression, and the 5-fluorouracil pathway were common but were not associated with specific types of pancreatic cancer.

Abstract ED01-01: Overview of biorepository best practices

Abstract There is considerable heterogeneity in the way that patients’ biospecimens (tissues, blood, urine for example) are collected, processed and stored in biorepositories. This unknown or uneven quality of biospecimens used for research can lead to unreliable and irreproducible results. In addition to technical and operational issues, many ethical, legal and policy guidelines and concerns must be addressed when conducting research involving the use of biospecimens from cancer patients and other research participants. After an extensive review of its own biorepostories, in 2007 the NCI Office of Biorepositories and Biospecimen Research (OBBR) published the NCI Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/practices/). The Best Practices do not comprise detailed procedures and are intended to be adapted, as appropriate, based on the mission and scientific needs of the individual biorepository. The technical best practices include recommendations for the collection, processing, storage and shipping of biospecimens, as well as quality control of processes and the proper collection of clinical data. The ethical, legal and policy practices provide guidance on informed consent, privacy and confidentiality, custodianship and intellectual property concerns. In response to questions and comments from the research community a new version of the Best Practices is being published in 2011. Major revisions include the addition of sections on biorepository management and operations and conflicts of interest, and expansion of recommendations related to custodianship and informed consent, harmonization with current Federal guidance documents and recommendations from international organizations. The revised Best Practices will be launched using an interactive web format, to provide a mechanism for more frequent updates and to encourage feedback from the community. The Best Practices will continue to evolve as the field of biospecimen biology advances; novel scientific, technological and clinical practices develop; and new ethical and legal policies and regulations emerge. The NCI is committed to maintaining current and scientifically accurate best practices for biorepositories and will continue to solicit input from stakeholders in the cancer research community. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):ED01-01.

SWOG Cooperative Group Biorepository Resource: Access for Scientific Research Studies

SWOG (formerly the Southwest Oncology Group), a National Cancer Institute-supported cooperative group, conducts multi-institutional, multidisciplinary clinical trials for adult patients with cancer, covering a wide range of solid tumors and hematologic cancers. The group has amassed a large set of biospecimens, collected from patients in numerous studies over many years and linked to clinical data. SWOG is now actively promoting the use of this unique scientific resource by making it available to a much wider group of researchers. This biospecimen resource offers material for research on disease mechanisms, genomic changes associated with cancer progression, markers of response and resistance to therapies, diagnosis or detection of recurrence, and more. By collecting, storing, and distributing the specimens, SWOG provides the framework for translational scientists to complete the feedback loop from "bedside to bench." This article provides an overview of the group's biospecimen resources and guidelines for gaining access to them.

An NCI Perspective on Creating Sustainable Biospecimen Resources

High-quality biospecimens with appropriate clinical annotation are critical in the era of personalized medicine. It is now widely recognized that biospecimen resources need to be developed and operated under established scientific, technical, business, and ethical/legal standards. To date, such standards have not been widely practiced, resulting in variable biospecimen quality that may compromise research efforts. The National Cancer Institute (NCI) Office of Biorepositories and Biospecimen Research (OBBR) was established in 2005 to coordinate NCI's biospecimen resource activities and address those issues that affect access to the high-quality specimens and data necessary for its research enterprises as well as the broader translational research field. OBBR and the NCI Biorepository Coordinating Committee developed NCI's "Best Practices for Biospecimen Resources" after consultation with a broad array of experts. A Biospecimen Research Network was established to fund research to develop additional evidence-based practices. Although these initiatives will improve the overall availability of high-quality specimens and data for cancer research, OBBR has been authorized to implement a national biobanking effort, cancer HUman Biobank (caHUB). caHUB will address systematically the gaps in knowledge needed to improve the state-of-the-science and strengthen the standards for human biobanking. This commentary outlines the progressive efforts by NCI in technical, governance, and economic considerations that will be important as the new caHUB enterprise is undertaken.

Assessing the Need for a Standardized Cancer HUman Biobank (caHUB): Findings From a National Survey With Cancer Researchers

Before developing a national standardized cancer HUman Biobank (caHUB), the National Cancer Institute sought feedback from the cancer research community. NCI conducted an online survey (N = 727) about current biospecimen needs and reactions to creating a national resource cancer researchers and others. Most (56%) participants obtained biospecimens within their own institutions, and 63% wanted more information about their biospecimens. Large proportions reported difficulty obtaining biospecimens of adequate numbers (39%) and quality (47%). Low-quality biospecimens resulted in 60% questioning their findings and 81% limiting the scope of their work. Nine in every 10 (91.3%) respondents reacted positively to the idea of a national biospecimen resource, with 62% reporting that they would obtain biospecimens from it and 53% reporting that they would be willing to contribute biospecimens to it. Initial reactions to caHUB were positive and seen as a feasible option to addressing respondents' research challenges. National Cancer Institute will need to address several concerns to assure its adoption, including standardization and sustainability.

Genome-wide interaction study of gemcitabine treatment and genotype on survival in pancreatic cancer.

4022 Background: Gemcitabine (gem) is commonly given for all stages of pancreatic adenocarcinoma (PC). However, it is not known a priori which patients will benefit from gem treatment compared to other treatments such as FOLFIRINOX. It is possible that germline variation may influence the efficacy of gem. Therefore, we performed a treatment-benefit interaction study of gem exposure with genome-wide single nucleotide polymorphisms (SNPs) on PC survival. Methods: We performed a two-stage cohort survival study of PC patients from the Mayo Clinic Pancreas Biospecimen Resource from 2000-08. In the first stage, we assessed data on 550,000 SNPs from 413 pts [median age 68, 56% male, 35%/34%/31% resected/locally advanced/metastatic (R/LA/M)] with PC for a Cox regression analysis assessing the interaction of gem treatment (Y/N) and genotype on survival, adjusted for age, stage, sex, and BMI. SNPs were also correlated with treatment toxicity. The 100 most significant SNPs from this first stage were used for a replication study of another 527 pts (median age 65, 53% male, 34%/32%/33% R/LA/M). Survival was assessed from first diagnosis to death (84% had died), and only patients with complete treatment records were included. Results: Nine SNPs interact with the same direction of effect (Table), including genes affecting apoptosis, reactive oxygen species, and other genes. PYCARD and MAPRE2 were strongly significant in both stages. MAPRE2, EPHB1, and NOX4 expression have previously been reported to affect chemosensitivity in pancreatic cancer cells in vitro. Conclusions: In a two-stage study, multiple SNPs appear to be predictive of the efficacy of gem therapy. No effects on gem toxicity were identified. SNP Gene Adjusted p value for interaction variable of genotype and gem exposure on survival Stage I (N=413) Stage II (N=527) Combined (N=940) rs6507115 MAPRE2 1.81 x 10-6 1.5 x 10-3 4.8 x 10-9 rs497279 NOX4 1.6 x 10-5 0.02 5.8 x 10-8 rs8056505 PYCARD 6.1 x 10-5 9.1 x 10-4 1.97 x 10-7 rs4889426 PLCG2 4.0 x 10-6 0.04 3.1 x 10-7 rs1021584 LOC100131418 4.5 x 10-5 0.03 5.9 x 10-7 rs7243052 PARD6G 2.5 x 10-4 0.01 2.7 x 10-6 rs1457784 KCNQ3 2.4 x 10-6 0.03 4.0 x 10-6 rs11130399 CACNA2D3 1.9 x 10-5 0.02 5.5 x 10-6 rs36064 EPHB1 3.6 x 10-4 0.04 1.5 x 10-5

Abstract 4660: The National Cancer Human Biobank: CaHUB

Abstract The Cancer Human Biobank (caHUB) is the first centralized and public biorepository for human biospecimens in the United States. Established by the National Cancer Institute (NCI) Office of Biorepositories and Biospecimen Research (OBBR), caHUB builds upon the foundation of evidence-based biospecimen resource management practices established by the OBBR Biospecimen Research Network (BRN) and the NCI Best Practices for Biospecimen Resources. The mission of the caHUB is to ensure an adequate and continuous supply of high-quality, highly annotated human biospecimens and provide unique biobanking services for the cancer research community. With a goal of fostering collaboration, communication, education, and the public trust, caHUB will be established as a public-private partnership, working with the broader cancer community, including basic and clinical researchers, advocacy organizations, and pharmaceutical and biotechnology companies. caHUB is a unique centralized biospecimen resource. In response to input from the scientific community, caHUB is focused on providing biospecimens and data collected according to the highest technical and ethical standards, developing biospecimen reference samples that serve as benchmarks for specimen integrity and molecular type, conducting research that supports evidence-based biospecimen best practices, and creating opportunities for collaboration and information exchange across the research enterprise. Through caHUB, the NCI seeks to address the shortage of highly-annotated research biospecimens collected under rigorous standards too costly for private organizations to pursue but required to address difficulties in validation of human biospecimen research results for scientific and regulatory purposes. caHUB is actively seeking the involvement of the cancer research community and supports engagement through three models of collaboration: 1) as customers seeking access to caHUB‘s Biospecimen Collections and Services; 2) as collaborative research partners who require caHUB to assist with specimen collections and analysis; and 3) as partners interested in information exchange with or financial support of this public initiative. For all interested parties, more information is available at http://cahub.cancer.gov. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4660. doi:10.1158/1538-7445.AM2011-4660

The Western Australian Melanoma Health Study: Study design and participant characteristics

Background: Cutaneous malignant melanoma is a major public health issue in Australia and other nations. A greater understanding of the genetic determinants and their interactions with environmental factors may lead to better interventions and control of the disease. The Western Australian Melanoma Health Study (WAMHS) is a population-based case-collection and biospecimen resource established to investigate the genetic epidemiology of melanoma. This manuscript discusses the design of the WAMHS and the characteristics of the participants. Methods: Participants were recruited through the Western Australian Cancer Registry, which is notified of all incident cancers in the state of Western Australia by law. Once the diagnosing doctor's consent was obtained, all eligible, resident Western Australian, adult cases of melanoma diagnosed between January 2006 and September 2009, were contacted by mail and invited to participate. Clinical, questionnaire-based phenotypic and blood samples for extraction of DNA, RNA and serum were collected from consenting cases. Clinical data consisted of all pathological data recorded by the cancer registry and the questionnaire, administered by telephone interview, covered major risk factors for melanoma, such as sun exposure history and skin type. Results: The final sample consisted of 1643 consenting cases out of 3420 cancer notifications (48.04%), of which 1455 cases completed one or more components of the study and 1157 completed all components. The WAMHS sample differed to all melanoma notifications only in age, with a bias towards older individuals (P<0.0001). No significant differences were observed in sex, melanoma site, Breslow thickness or Clark's level. Conclusions: The WAMHS study is novel in its non-family based approach and focus on common (low penetrance) genetic determinants. This comprehensive resource will enable further steps to be taken towards understanding the complex pathways involved in melanoma.

CaTissue Suite: An Open‐Access, Feature‐Rich Tool For Biospecimen Annotation And Data Sharing

Advances in molecular technologies and clinical trial design have mandated new requirements for the operation of biorepostories. caTissue Suite is a caBIG(TM) application designed to manage the complexities of biospecimen annotation data.caTissue Suite is a software application developed with requirements gathering and acceptability testing by multiple institutions. caTissue uses a web browser to store and retrieve data from a database. Its open program interface (API) permits customized access to all of the application's features, and data integration from other data systems.caTissue Suite is scalable and configurable for broad deployment across biorepostories of varying size and function. Numerous institutions have adopted the application and are using it in their daily operations. A caBIG(TM) supported, web‐based “Knowledge Center” (https://cabig‐kc.nci.nih.gov/Biospecimen/KC) provides on‐going application support via discussion forums, technical and user guides, training tools, and webinars.caTissue Suite is a freely available, fully supported, open‐access software application for biospecimen data management. Use of caTissue Suite by several NCI Cancer Centers and other biospecimen resource groups is providing a rapid and facilitated path toward standardizing biospecimen informatics and promoting biospecimen data sharing both nationally and globally.

Patterns of Pancreatic Resection Differ Between Patients with Familial and Sporadic Pancreatic Cancer

BackgroundAlthough the increased risk of developing pancreatic cancer (PC) in families with a strong history of the disease is well known, characteristics and outcomes of patients with familial PC is not described well. AimsThis study aims to evaluate outcomes following resection in patients with familial PC. MethodsWe studied 208 patients who underwent resection of PC from 2000 to 2007 and had prospectively completed family history questionnaires for the Biospecimen Resource for Pancreas Research at our institution. We compared clinical characteristics and outcomes of familial and sporadic PC patients. ResultsFamilial (N = 15) and sporadic PC patients (N = 193) did not have significantly different demographics, pre-operative CA19-9, pre-operative weight loss, R0 status, or T-staging (all p ≥ 0.05). Familial PC patients had lower pre-operative total serum bilirubin concentrations (p = 0.03) and lesions outside of the pancreatic head more frequently (p = 0.02) than sporadic PC patients. There was no difference in survival at 2 years between familial and sporadic PC patients (p = 0.52). ConclusionsFamilial PC patients appear to develop tumors outside of the pancreatic head more frequently than sporadic PC patients. This difference in tumor distribution may be due to a broader area of cancer susceptibility within the pancreas for familial PC patients.

Abstract 969: Revising and updating NCI's best practices for biospecimen resources

Abstract In 2007 the NCI Office of Biorepositories and Biospecimen Research (OBBR) published the NCI Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/practices/). The Best Practices were originally published following a public comment period on the Federal Register and internal review by several National Institutes of Health offices. The Best Practices do not comprise detailed laboratory procedures and are intended to be adapted, as appropriate, based on the mission and scientific needs of individual biospecimen resources. The Best Practices were developed to address the heterogeneity and the generally unknown or uneven quality of biospecimens used for research, which can lead to unreliable and irreproducible results. In addition to these technical and operational issues, many ethical, legal and policy guidelines and concerns must be addressed when conducting research involving the use of biospecimens from patients and other research participants. The revised version of the Best Practices is intended to respond to comments received from the biospecimen resource community over the past 2 years, and provide more current and detailed recommendations related to biospecimen and data quality. Major revisions include the addition of new sections on biospecimen resource management and operations and conflicts of interest, and expansion of recommendations related to custodianship and informed consent based on the consensus findings of the 2007 NCI-hosted Workshop on Custodianship and Ownership Issues in Biospecimen Research, addition of current references throughout the document, and harmonization with current Federal guidance documents and recommendations from international biospecimen organizations. The revised Best Practices will be launched using an interactive Web format, to provide a mechanism for more frequent updates and encourage feedback from the community. The Best Practices will continue to evolve as the field of biospecimen biology advances; novel scientific, technological, and clinical practices develop; and new ethical and legal policies and regulations emerge. Results from biospecimen research initiatives will inform future versions of the Best Practices as the community moves toward the development of evidence-based standard operating procedures that are both specimen type specific and analysis platform specific. The NCI is committed to maintaining current and scientifically accurate best practices for biospecimen resources and will continue to solicit input from stakeholders in the cancer research community. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 969.

Abstract 984: Planning for caHUB, NCI's cancer human biobank

Abstract Many high-profile NCI initiatives are significantly impacted by biospecimen availability and quality. One of the newly delineated developmental pathways for transforming scientific discoveries into new clinical modalities for oncology, defined by NCI's Translational Research Working Group, is entirely biospecimen-based and is similarly impacted. Both direct experience with these initiatives as well as broader input from the scientific community, including recent results from a market research survey, have indicated a striking unmet need for high-quality human biospecimens. In response to this need, the Office of Biorepositories and Biospecimen Research (OBBR) is planning for the implementation of the cancer Human Biobank (caHUB). No centralized resource of this type exists at this time. This initiative will take advantage of resources already developed by the NCI, including the OBBR Biospecimen Research Network (BRN) and the NCI Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/practices/). The OBBR is engaging in a detailed process with a variety of planning groups, to address the requirements for implementation of caHUB. caHUB will acquire and make available to the research community biospecimens that have been collected according to the highest technical and ethical standards; provide biospecimen reference samples that serve as benchmarks for specimen integrity and molecular type; conduct research that supports evidence-based biospecimen best practices; and create opportunities for collaboration and information exchange across the research enterprise. caHUB will ensure the quality of its inventory by acquiring biospecimens that have been collected and processed according to evidence-based standard operating procedures, annotated with comprehensive clinical, molecular, and collection data, and procured from patients who received high-quality care. caHUB proposes to contract with military, community, and academic institutions to collect biospecimens and their associated data. Through a caBIG®-compliant public network, caHUB will make specimens and data available to a broad research community, including academia, government, private foundations, and biotechnology and pharmaceutical industries, and enable new collaborations among researchers in all areas of investigation, thereby accelerating the pace of discovery and innovation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 984.

Abstract 973: The NCI Biospecimen Research Network

Abstract The National Cancer Institute's (NCI) Office of Biorepositories and Biospecimen Research (OBBR) initiated the Biospecimen Research Network (BRN) in early 2006 to coordinate and support systematic investigation into how collection, processing, and storage of human biospecimens affect subsequent analysis. To support this goal, the BRN sponsors, conducts and collaborates on studies to evaluate the effects of biospecimen pre-analytical variables on the outcomes of molecular assays for cancer diagnosis and research. BRN supported findings will contribute to the development of evidence-based best practices for the collection, processing, storage and transport of biospecimens; building on the “NCI Best Practices for Biospecimen Resources.” Currently the BRN sponsors a variety of initiatives aimed to develop and support the research efforts of the biospecimen science community. Through its newly launched extramural research program the BRN supports a portfolio of projects addressing biospecimen pre-analytical variables and biospecimen integrity. Furthermore, the BRN aims to significantly improve biospecimen-based diagnostic and research capabilities by communicating the results of such research to the scientific and clinical communities. The Biospecimen Research Database and the annual BRN symposium, Advancing Cancer Research Through Biospecimen Science are forums established for effective exchange of biospecimen research results. The BRN also supports new research and innovation through its collaborations with other NCI programs such as NCI Innovative Molecular Analysis Technologies (IMAT), the NCI Small Business Innovation Research Development Center (SBIR), the Clinical Proteomics Technologies for Cancer (CPTC) and the Cancer Genome Atlas (TCGA). Through these partnerships, the BRN serves as a resource for program awardees and presents new opportunities for research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 973.

Fluorescence in situ hybridization to visualize genetic abnormalities in interphase cells of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.

To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas. Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS. These FISH probes were used with control probes to distinguish among various kinds of chromosome abnormalities of number and structure. FISH abnormalities were observed in 12 (80%) of 15 patients with pancreatic cancer: 5 of 5 patients with acinar cell carcinoma, 5 of 5 patients with ductal adenocarcinoma, and 2 (40%) of 5 patients with islet cell carcinoma. All 3 specimens of pancreatic tissue without neoplasia had normal FISH results. Gains of CTNNB1 due to trisomy 3 occurred in each tumor with acinar cell carcinoma but in none of the other tumors in this study. FISH abnormalities of all other cancer genes studied were observed in all forms of pancreatic tumors in this investigation. FISH abnormalities of CTNNB1 due to trisomy 3 were observed only in acinar cell carcinoma. FISH abnormalities of genes implicated in familial cancer, tumor progression, and the 5-fluorouracil pathway were common but were not associated with specific types of pancreatic cancer.