bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2553: High-density array-CGH with targeted NGS unmask multiple non-contiguous minute deletions on chromosome 3p21 in mesothelioma
Authors: Carbone Michele , Yoshikawa Yoshie , Emi Mitsuru , Hashimoto-Tamaoki Tomoko , Ohmuraya Masaki , Sato Ayuko , Tsujimura Tohru , Hasegawa Seiki , Nakano Takashi , Nasu Masaki , Pastorino Sandra , Szymiczek Agata , Bononi Angela , Pass Harvey I. , Yang Haining 
Published: July 2017

Abstract
We used a custom-made comparative genomic hybridization-array (aCGH; average probe interval 254 bp) to screen 33 malignant mesothelioma (MM) biopsies for somatic copy number loss throughout the 3p21 region (10.7 Mb) that harbors 251 genes, including BRCA1-associated protein 1 (BAP1), the most commonly mutated gene in MM. We identified frequent minute biallelic deletions (&lt;3 Kb) in 46/251 genes: four were cancer associated genes: SETD2 (7/33), BAP1 (8/33), PBRM1 (3/33) and SMARCC1 (2/33). These four genes were further investigated by targeted Next Generation Sequencing (tNGS), which revealed sequence-level mutations causing biallelic inactivation. Combined high-density aCGH and tNGS revealed biallelic gene inactivation in SETD2 (9/33, 27%), BAP1 (16/33, 48%), PBRM1 (5/33, 15%) and SMARCC1 (2/33, 6%). The incidence of genetic alterations detected is much higher than reported in the literature because minute deletions are not detected by NGS or commercial aCGH. Many of these minute deletions were not contiguous but rather they alternated with segments showing oscillating copy number changes along the 3p21 region. Functional assays revealed that SETD2, PBRM1 and SMARCC1 act as tumor suppressor in MM. In summary, we found that in MM: 1) multiple minute simultaneous biallelic deletions are frequent in chromosome 3p21, where they occur as distinct events involving multiple genes; 2) in addition to BAP1, mutations of SETD2, PBRM1 and SMARCC1 are frequent in MM; 3) our results suggest that high-density aCGH combined with tNGS provide a more precise estimate of the frequency and types of genes inactivated in human cancer, than approaches based exclusively on NGS strategy.
Citation Format: Michele Carbone, Yoshie Yoshikawa, Mitsuru Emi, Tomoko Hashimoto-Tamaoki, Masaki Ohmuraya, Ayuko Sato, Tohru Tsujimura, Seiki Hasegawa, Takashi Nakano, Masaki Nasu, Sandra Pastorino, Agata Szymiczek, Angela Bononi, Harvey I. Pass, Haining Yang. High-density array-CGH with targeted NGS unmask multiple non-contiguous minute deletions on chromosome 3p21 in mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2553. doi:10.1158/1538-7445.AM2017-2553
Abstract 2567: CYP24A1-induced vitamin D insufficiency promotes breast cancer growth
Authors: Osanai Makoto , Takasawa Akira , Takasawa Kumi , Murata Masaki , Sawada Norimasa 
Published: July 2017

Abstract
Vitamin D plays a critical role in the maintenance of tissue homeostasis by regulating the expression of genes affecting cell proliferation, differentiation, and apoptosis. The vitamin D 24-hydroxylase CYP24A1 functions in vitamin D target tissues to degrade the hormonal form of vitamin D. Existing knowledge regarding dysregulated CYP24A1 expression supports its candidacy as a putative oncogene. In our presentation, we demonstrate that the suppression of constitutive CYP24A1 expression by CYP24A1-specidic shRNA conferred target cells with increased susceptibility to apoptosis and consequently inhibited anchorage-independent growth in breast carcinoma cells. In addition, suppression of vitamin D metabolism following knockdown of CYP24A1 significantly reduced tumor growth in vivo. Since these data provide substantial evidence for a pro-survival and stimulatory oncogenic effect of CYP24A1 in breast carcinoma cells, we will discuss the potential feasibility of CYP24A1-inhibitory cancer therapies.
Citation Format: Makoto Osanai, Akira Takasawa, Kumi Takasawa, Masaki Murata, Norimasa Sawada. CYP24A1-induced vitamin D insufficiency promotes breast cancer growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2567. doi:10.1158/1538-7445.AM2017-2567
Abstract 256A: Validation of methyl donors between two food measurements in a colorectal cancer study
Authors: Young Lufei , Shiao S. Pamela K. 
Published: July 2017

Abstract
Purpose: The purpose of this study was to validate methyl donor intakes between 30-day food frequency questionnaire (FFQ) and 24-hour food record (FR) in a colorectal cancer study.
Background: Dietary methyl donors play pivotal roles in cancer prevention by promoting adequate metabolism and DNA methylation. The FFQ and 24-hour FR are the most commonly used methods to assess adequate nutrient intake, including methyl donors and other vital micronutrients that are essential to promote metabolism and methylation. While FFQ provides best estimates in dietary intakes, a 24-hour food record is less time consuming for subject burden.
Methods: A total of 134 participants’ dietary data were collected using FFQ and 24-hour FR by using US Department of Agriculture computerized programs. Bland and Altman methodology was used to validate the bias and agreement between these two measurements.
Results: Overall, the 24-hour measurements presented underestimated values across all nutrients in comparison to FFQ measurements. Using a 10% criterion on the differences between the two measurements, the percentage bias for 24-hour FR compared to 30-day FFQ was acceptable for most B vitamins, including B1 (-6.9 ±0.15), B2 (-8.66± 0.12), B3 (-9.25± 0.12), B6 (-5.02, ± 0.14), and B9 (folate: -7.90 ±0.24). However, the bias was greater for protein based methyl donors, including B12 (-17.23± 0.14), choline (-13.38± 0.11), Glycine (-17.53± 0.10), and Methionine (-18.88± 0.09). The correlations between the two measurements on all methyl donors ranged from 0.92 to 0.99. The precisions for all measurements based on the standard error (SE) were less than and within 0.03% (0.007 -0.021%). And, the agreements between the two measurements were less than and within 10% for Glycine and methionine (8.96 - 9.58%), based on the standard deviation (SD); however, greater than 10% for other protein based methyl donors including choline and other B vitamins (10.5-24.11%).
Conclusion: Proper dietary intakes of methyl donors are vital for cancer prevention. These findings point out the importance of further validation and use of more accurate food measurement to monitor dietary intake, and the interpretation of nutrient reports with caution.
Citation Format: Lufei Young, S. Pamela K. Shiao. Validation of methyl donors between two food measurements in a colorectal cancer study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 256A. doi:10.1158/1538-7445.AM2017-256A
Abstract 2572: The novel long non-coding RNA PANCR is an intracellular p53 activator
Authors: Cao Yu 
Published: July 2017

Abstract
Long non-coding RNAs (LncRNAs) function as oncogenes or tumor suppressors in development and progression of cancer. Chromosome 16q22.1 region is frequently deleted in breast cancer, which may contribute to breast carcinogenesis by inactivation of tumor suppressor genes. This study characterized a new LncRNA tumor suppressor, named p53 activating non-coding RNA (PANCR), located in this Chromosome 16q22.1 region. This PANCR LncRNA consists of 1.5kb in length.Our data showed that PANCR was downregulated in breast cancer cell lines and tissues. In the breast cancer cell lines, PANCR expression appeared reversely correlated with cell malignancy, and in breast cancer tissues, PANCR was downregulated over 2 times in 31(62.0%) of 50 cases when compared to adjacent normal breast tissues. In breast cancer cells MCF7 and immortalized human mammary epithelial cells MCF10A, ectopic expression of PANCR induced marked apoptosis, suppressing cell proliferation in culture and tumor growth in xenografts, but in contrast, shRNA-mediated silencing of PANCR promoted cell growth and proliferation. Mechanistic approaches revealed that in both MCF7 and MCF10A cell, PANCR activated p53 and upregulated pro-apoptotic proteins bid and bim and cell cycle inhibitors p21waf/cip1 and p27Kip1. We further explored the mechanism of action that PANCR activates p53, and our results from RNA immunoprecipitation (RIP), RNA pulldown and immunoprecipitation (Co-IP) demonstrated that the PANCR can bind to p53, dissociate p53-MDM2 complex and thus activate p53.Together our data suggest that the novel LncRNA PANCR located in the deleted Chromosome 16q22.1 region is an intracellular p53activator, functioning as a tumor suppressor by activating p53-mediated apoptosis.
Citation Format: Yu Cao. The novel long non-coding RNA PANCR is an intracellular p53 activator [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2572. doi:10.1158/1538-7445.AM2017-2572
Abstract 2583: A model for capturing and integrating complex molecular alterations related to clinically relevant efficacy evidence
Authors: Statz Cara M. , Patterson Sara E. , Yin Taofei , Mockus Susan M. 
Published: July 2017

Abstract
The ability to capture data relevant to different types of oncology-related variations, including single nucleotide variations, deletions, insertions, copy number variations, and fusions in a single system is crucial to a comprehensive understanding of cancer biology. However, collectively linking these varied types of molecular alterations to capture their compound impact to clinically relevant efficacy evidence within a database can prove challenging. Thus, we have built the JAX Clinical Knowledgebase (JAX-CKB), a flexible relational database that allows curation of complex molecular profiles and provides the ability to associate these profiles with documented efficacy evidence, thereby providing a more detailed overview of therapeutic relevance. To demonstrate the utility of creating complex molecular signatures in relation to efficacy evidence, the JAX-CKB was queried to first determine the overall degree of efficacy evidence content related to complex profiles. Additionally, two specific types of complex molecular profiles were queried, which included EML4-ALK plus a missense mutation(s) and BRAF V600E plus any type of molecular alteration(s). Within the JAX-CKB, there are 1,383 unique efficacy evidence lines linked to complex molecular profiles. The complex molecular profiles consisting of EML4-ALK and one or more additional missense mutations were associated with 174 unique efficacy evidence lines. Of the 174 lines, 69 were annotated with a resistant response type, while 68 were annotated with a sensitive response type. The combination of BRAF V600E with one or more molecular alterations was linked to 229 unique efficacy evidence lines. The majority of the lines, 118, were specific to a resistant response type and 83 were associated with sensitivity. Comprehensive genomic profiling of cancer patient samples can often reveal complex molecular signatures. The JAX-CKB is an inclusive knowledgebase that allows one to interpret these complex signatures and rapidly identify appropriate targeted therapies, which could be critical in a clinical setting.
Citation Format: Cara M. Statz, Sara E. Patterson, Taofei Yin, Susan M. Mockus. A model for capturing and integrating complex molecular alterations related to clinically relevant efficacy evidence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2583. doi:10.1158/1538-7445.AM2017-2583
Abstract 2589: Identifying cancer susceptibility variants and genes using whole exome and genome sequencing: a literature review
Authors: Rotunno Melissa , Clyne Mindy , Lam Tram , Mechanic Leah , Daee Danielle , Nelson Stefanie , Gillanders Elizabeth , Goldstein Alisa 
Published: July 2017

Abstract
The application of Next Generation Sequencing (NGS) technologies in cancer research enabled the discovery of novel somatic mutations at an unprecedented speed through efficient high-throughput profiling of DNA variation in tumor samples. In contrast, the identification through NGS studies of germline variation associated with cancer has been more difficult and with limited consensus around best practices for study design and analytical techniques. We performed a review of the 2005-2016 PubMed English literature for genome-wide germline sequencing studies that were aimed at identifying new cancer susceptibility genes or variants. We extracted and summarized the experimental and analytical designs, methods and tools implemented in the selected literature together with their degree of success and limitations in identifying cancer susceptibility variants. About 80 in-scope publications were identified and examined in depth. The most studied cancer types were colorectal, breast, blood and lung and were investigated predominantly via whole exome sequencing (primarily using Illumina HiSeq) in familial cases of Caucasian ethnicity. Only 10 studies used whole genome sequencing and 15 adopted a case control study design. A large fraction of the familial studies was limited to 1 or 2 families and sequenced 2 or less cases per family. Reporting of key data quality information (e.g., human sequence coverage) was inconsistent throughout the publications. While the methods for sequence alignment and variant calling converged towards those implemented in established bioinformatic tools (e.g., BWA, GATK), there were no standard approaches for filtering or prioritizing of variants. Most studies included some degree of technical validation, often restricted to the top few variants or genes. About 60% of the studies included replication in an independent group of cancer patients and 55% functionally validated their findings to some extent. Our work provides valuable data and insights to inform future sequencing studies of cancer genetic susceptibility, and points to the need for improving standardization and completeness in reporting of quality control metrics, study design rationale and interpretation of findings.
Citation Format: Melissa Rotunno, Mindy Clyne, Tram Lam, Leah Mechanic, Danielle Daee, Stefanie Nelson, Elizabeth Gillanders, Alisa Goldstein. Identifying cancer susceptibility variants and genes using whole exome and genome sequencing: a literature review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2589. doi:10.1158/1538-7445.AM2017-2589
Abstract 2591: A guide to filtering TARGET Complete Genomics germline variants
Authors: Evans James P. , Patidar Rajesh , Vaksman Zalman , Sindiri Sivasish , Stewart Douglas R. , Khan Javed , Wei Jun S. , Diskin Sharon J. 
Published: July 2017

Abstract
With the public release of TARGET’s pediatric cancer data, researchers are eager to investigate and integrate variants from both tumor and germline sequencing data, but caution should be used when interpreting TARGET variant calls from Complete Genomics data, as they unlike the Illumina based calls for which most of our databases and tools are customized. Here, we use germline samples from 55 neuroblastoma cases with both whole genome Complete Genomics variants and whole exome Illumina variants from GATK, Pindel, Platypus, and bam2mpg to investigate differences between germline variant calls from Complete Genomics and Illumina platforms. Our study of ~160,000 single nucleotide polymorphisms (SNPS) and ~19,000 insertions or deletions (indels) reveals that while SNP sets largely agree between Complete Genomics and Illumina, Complete Genomics data have many indels not present in Illumina calls, making it difficult to screen Complete Genomics indels against popular Illumina based variant databases like those provided by the Exome Aggregation Consortium and the National Heart, Lung, and Blood Institute Exome Sequencing Project. Further probing of Complete Genomics indels uncovered inconsistent indel formatting resulting a loss of recurrent variants, and miscalculated read depths in earlier versions of the Complete Genomics platform. To solve these issues and make Complete Genomics variant calls comparable to Illumina calls, we introduce a Snakemake pipeline that reformats Complete Genomics variant files and creates variant features for use in decision tree or random forest classifiers trained to recognize Complete Genomics variants that will be present in Illumina variant call sets. We determine that the most important features for locating Complete Genomics variants likely to be found in Illumina germline variant call sets are the presence of reads from both directions, average variant allele fraction across the cohort, a variant call in the matched tumor, the variant fraction of reads, and read depth. Using ten fold cross validation with our decision tree, we obtain &gt;95% recall and &gt;98% precision for SNPs, and &gt;90% recall and &gt;85% precision for indels. We advocate the use of our pipeline and filtering scheme for making Complete Genomics variant calls comparable to Illumina based calls.
Citation Format: James P. Evans, Rajesh Patidar, Zalman Vaksman, Sivasish Sindiri, Douglas R. Stewart, Javed Khan, Jun S. Wei, Sharon J. Diskin. A guide to filtering TARGET Complete Genomics germline variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2591. doi:10.1158/1538-7445.AM2017-2591
Abstract 2599: COSMIC Cancer Gene Census: expert descriptions across genes in oncogenesis
Authors: Sondka Zbyslaw , Bamford Sally , Cole Charlotte G. , Dawson Elisabeth , Ponting Laura , Stefancsik Raymund , Ward Sari A. , Tate John , Campbell Peter J. , Forbes Simon A. 
Published: July 2017

Abstract
The Cancer Gene Census is an ongoing effort to catalogue genes for which somatic mutations have been causally implicated in cancer. The Census comprises manually curated summaries of the most relevant information for cancer-driving genes and their somatic mutations and brings together the expertise of a dedicated curation team, cancer scientists and the comprehensive resources of the COSMIC database. Current research focuses on characterising the participation of 609 census genes in hallmarks of cancer and identification of additional genes involved in these biological traits primarily via altered expression, CNA or epigenetic changes. New overviews of cancer gene function focused on hallmarks of cancer pull together manually curated information on the function of proteins coded by cancer genes and summarises the data in simple graphical form. It presents a condensed overview of most relevant facts with quick access to the literature source, aiming to provide summary characteristics of a cancer gene, rather than a full monography, to avoid information overload. This functional characterisation enables the creation of lists of genes of interest focused on the particular role they play in the development of cancer, as well as aiming to identify the cellular functions affected by mutations in particular tumours, and help to choose right targets for targeted therapy or synthetic lethality experiments. The Census is available from the COSMIC website for online use or download at: http://cancer.sanger.ac.uk/census.
Citation Format: Zbyslaw Sondka, Sally Bamford, Charlotte G. Cole, Elisabeth Dawson, Laura Ponting, Raymund Stefancsik, Sari A. Ward, John Tate, Peter J. Campbell, Simon A. Forbes. COSMIC Cancer Gene Census: expert descriptions across genes in oncogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2017-2599
Abstract 26: Panitumumab interacts with TAS-102 leading to combinational anti-cancer effects by blocking EGFR-mediated tumor response to trifluridine
Authors: Nakamura Kazuhide , Baba Yuji , Tamura Toshiya , Satoh Yoshihiko , Gotou Masamitsu , Sawada Hiroshi , Ebara Shunsuke , Shibuya Kazunori , Soeda Jumpei 
Published: July 2017

Abstract
Panitumumab is a monoclonal antibody raised against the human epidermal growth factor receptor (EGFR). TAS-102 is a novel chemotherapeutic agent containing trifluridine (FTD) as the active cytotoxic component. Both panitumumab and TAS-102 have been approved for the treatment of metastatic colorectal cancer (mCRC). In this study, we show the mechanism underlying the anti-cancer effects of the panitumumab/TAS-102 combination in preclinical models. Co-treatment with panitumumab and FTD exerted additive and synergistic anti-proliferative effects in LIM1215 and SW48 colon cancer cells, respectively. Consistent with the in vitro effects, panitumumab/TAS-102 combination led to tumor regression in LIM1215 and COL-01-JCK colon cancer patient-derived xenograft models. In LIM1215 cells, FTD induced ERK/Akt/STAT3 phosphorylation and subsequent serine/threonine phosphorylation of EGFR, while it had no effects on EGFR tyrosine phosphorylation. Panitumumab and the tyrosine kinase inhibitor erlotinib reduced the basal level of EGFR tyrosine phosphorylation and reversed the FTD-induced ERK/Akt/STAT3 and EGFR serine/threonine phosphorylation. These results suggested that FTD together with the basal activity of the EGFR tyrosine kinase induced downstream pro-survival signaling through ERK/Akt/STAT3. Collectively, we propose that panitumumab interacts with FTD by targeting EGFR-mediated adaptive responses, thereby exerting anti-cancer effects in combination with TAS-102. These preclinical findings provide a compelling rationale to evaluate anti-EGFR antibodies combined with TAS-102 against mCRC.
Citation Format: Kazuhide Nakamura, Yuji Baba, Toshiya Tamura, Yoshihiko Satoh, Masamitsu Gotou, Hiroshi Sawada, Shunsuke Ebara, Kazunori Shibuya, Jumpei Soeda. Panitumumab interacts with TAS-102 leading to combinational anti-cancer effects by blocking EGFR-mediated tumor response to trifluridine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 26. doi:10.1158/1538-7445.AM2017-26