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Shared scientific resources, also known as core facilities, support a significant portion of the research pursued in biomolecular research institutions. The Committee on Core Rigor and Reproducibility (CCoRRe) conducted a survey aimed at the scientific core community to gaininformation on how NIH initiatives on advancing scientific rigor and reproducibility have influenced current services and new technology development in shared scientific resources.In addition, the survey aimed to identify the challenges and opportunities scientific cores have related to implementation of new reporting requirements to identify new practices and resources needed to assure rigorous research. Presented is a rigorous re-analysis of the participants' responses and commentaries. Results revealed mixed perspectives and levels of awareness regarding the NIH guidelines. Many of the perceived challenges to the effective implementation of scientific rigor and reproducibility practices were similarly noted as challenge areas in effectively providing support services in a core setting. Further, most cores routinely use best practices and offer services that support rigor and reproducibility. These factors include access to well-maintained instrumentation, training on experimental design and data analysis, as well as data management. Feedback from the survey will enable the ABRF to build better educational resources and share critical best practice guidelines. ABRF sponsors a central information portal that can be expanded to provide timely information on meetings, training modules, online repositories and webinars supporting research integrity. These resources will provide important tools to the core community and the researchers they serve to positively impact rigor and transparency across the range of science and technology.

Embryonal rhabdomyosarcoma (ERMS) is the most prevalent pediatric soft tissue tumor and is characterized at the molecular level by loss of heterozygosity (LOH) at 11p15.5. We aimed to study ERMS in the context of Costello syndrome (CS), a rare syndromic predisposition to ERMS. Because CS arises from a typically paternal germline mutation in the proto-oncogene HRAS, it is considered a rasopathy. CS results in failure to thrive, intellectual disabilities, short stature, coarse facial features, skeletal abnormalities, congenital heart disease, and a predisposition for cancer, most commonly ERMS. Using the Biomolecular Core Laboratory technical expertise and Nemours clinical resources, we molecularly characterized eight ERMS tumors from six unrelated CS patients, carrying paternally derived HRASp.G12S (6) or p.G12A (2) mutations. LOH was evaluated in all CS ERMS tumors by microarray and/or using short tandem repeat (STR) markers along both arms of chromosome 11. One patient developed a second primary ERMS tumor showing the ERMS hallmark LOH limited to 11p15.5. The six other CS ERMS tumors displayed paternal uniparental disomy (UPD) of the entire chromosome 11. Paternal UPD was also observed in a pure ERMS cell line, established by our core lab using fresh tumor sample from one of the patients with a p.G12A germline mutation. This represents, to our knowledge, the first CS ERMS cell line in existence. Additional cell lines derived from non CS patients were used in this study and included three ERMS (RD, RH18 and RH36), one Alveolar RMS (RH30). RH36 cells carried an HRAS mutation at position 61 (p.Q61K). Unexpectedly, both ERMS cell lines, RD and RH36, displayed a complete LOH for chromosome 11. The ARMS RH30 cells carried no mutation in HRAS or LOH. RH18 cells derived from an ERMS had no HRAS mutation and showed LOH on both, the p and q arm of chromosome 11, except at locus D11S1338. Cytogenetic analysis with fluorescence in situ hybridization (FISH) on three CS tumors revealed multiple copies of chromosome 11 leading to trisomies and tetrasomies in the tumor and cultured cells. Gene expression analysis revealed loss of imprinting in the growth regulating genes H19, IGF2, and CDKN1C on chromosome 11 not only in CS tumors, but also in nonsyndromic ERMS. Elucidating the basis of tumor-specific activation/inactivation pathways in a core lab setting is providing important determinants in patient diagnosis and in novel therapeutic design. This work illustrates one of the critical roles a core laboratory may play when fully integrated in biomedical research endeavors.