bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2227: An automatic pipeline to find and annotate rare subclonal somatic variants in a paired tumor/normal sample
Authors: Joecker Anika , Pearson Nathan , Boysen Cecilie , Thomson Naomi , Hein Anne-Mette , Oster Bodil , Arens Anne , Knudsen Bjarne , Knudsen Thomas , Richards Dan , Forsberg Roald 
Published: May 2015

Abstract
Identifying and characterizing somatic variants in deep genome sequence data from tumor samples remains challenging and time-consuming. Of special interest in cancer research and diagnostics is the detection and annotation of rare subclonal somatic variants found only in a small proportion of primary tumor cells. Such variants can drive tumor spread and recurrence, but are often neglected in choosing treatments.
Currently, few tools reliably distinguish such rare subclonal variants from sequencing errors. And even among real somatic variants, drivers (of tumor growth, spread, or resistance) are hard to distinguish from passengers. Doing so entails integrating diverse information on variants, genes, pathways, cancer-relevant phenotypes, and treatments (including insights on population allele frequencies and broader evolutionary conservation; known/likely effects on gene product structure, function, expression, and interaction; and relations among gene products, phenotypes, and drugs). Software for effectively integrating such data in light of genomic variation in samples, to highlight relevant findings through clear visualization, has been a pressing need.
Here we present an end-to-end analysis workflow for finding and functionally characterizing rare subclonal variants, using the newly developed CLC Cancer Research Workbench to feed the interpretive platform of Ingenuity Variant Analysis, to identify cancer driver mutations in paired tumor/normal samples. We will show new interesting results from this analysis, which were not shown beforehand on this publicly available cancer dataset (Case Reports in Oncological Medicine, Volume 2013 (2013), Article ID 270362) from a patient with massive acinic cell carcinoma.
Citation Format: Anika Joecker, Nathan Pearson, Cecilie Boysen, Naomi Thomson, Anne-Mette Hein, Bodil Oster, Anne Arens, Bjarne Knudsen, Thomas Knudsen, Dan Richards, Roald Forsberg. An automatic pipeline to find and annotate rare subclonal somatic variants in a paired tumor/normal sample. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2227. doi:10.1158/1538-7445.AM2014-2227
Abstract 2230: Gene mutations and deletions inactivates PTEN tumor suppressor in Chilean colon cancer patients
Authors: Encina Gonzalo , Alvarez Karin , Orellana Paulina , Wielandt Ana María , Villarroel Cynthia , Simian Daniela , Contreras Luis , Kronberg Udo , López Francisco , Carvallo Pilar 
Published: May 2015

Abstract
Introduction. Tumor suppressor PTEN acts as a negative regulator of the PI3K/AKT/mTOR pathway, thus controlling cell survival and proliferation. Mutations or deletions inactivating PTEN function lead to over-activation of the PI3K/AKT/mTOR pathway in cancer. PTEN gene alterations have been described in different types of tumors. In colon cancer these mutations range from 1% to 29% of the cases. The aim of this study was to determine the prevalence of PTEN mutations and/or deletions in Chilean colon cancer patients. Methods: ninety-one colon cancer patients were recruited for this study. Genomic DNA from normal and tumor tissue was obtained, and the deletion of PTEN locus was determined by PCR amplification of three STR markers flanking PTEN, and two intragenic markers. To search point mutations we amplified exons 7 and 8 by PCR, and sequenced. PTEN expression was evaluated through immunohistochemistry. Results: We observed deletion events in 9.8% (9/91) of tumors, and inactivating mutations in 5.5% (5/91). Two tumors presented a deletion in one allele and a mutation in the other. Immunohistochemistry detected a very weak expression of PTEN in 55/76 tumors. Conclusions: 15.4 % (12/91) of tumors have PTEN gene inactivated. We observed that deletion was a frequent mechanism for PTEN inactivation in Chilean colon cancer patients.
Note: This abstract was not presented at the meeting.
Citation Format: Gonzalo Encina, Karin Alvarez, Paulina Orellana, Ana María Wielandt, Cynthia Villarroel, Daniela Simian, Luis Contreras, Udo Kronberg, Francisco López, Pilar Carvallo. Gene mutations and deletions inactivates PTEN tumor suppressor in Chilean colon cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2230. doi:10.1158/1538-7445.AM2014-2230
Abstract 2231: The prevalence of EGFR and KRAS mutations in a population of African immigrants in France is closer to that of Asian populations than to white Europeans
Authors: Lemoine Antoinette , Saffroy Raphael , Bosselut Nelly , Lecorche Emmanuel , Etessami Reza , Allard Marc A. , Tredaniel Jean , Balaton Andre , Validire Pierre , Morere Jean F. 
Published: May 2015

Abstract
The choice of treatment for patients with NSCLC relies on the EGFR and KRAS mutational status. Previous studies have reported differences in prevalence of mutations between Asiatics, Hispanics and Caucasians. However, there is few data with respect to the frequencies of EGFR and KRAS mutations in patients originated from Africa, who represent the largest immigrant population in France.
Between May 2011 and November 2013, a mutational analysis for KRAS and EGRF has been performed in tumor samples from 1,973 consecutive patients with NSCLC at a single oncogenetic platform. Demographic and clinical data of all these patients were extracted from their electronic medical record and analyzed.
Our study population included 1,739 (88%) white Europeans, 204 (10%) patients from Africa and 30 (2%) patients from Asia (mostly from Vietnam or Cambodge).
As expected, the higher prevalence of EGFR mutations was found in Asiatic women (50%), the lower was observed in Caucasian women population (17%, p&lt;0.001). This low frequency of EGFR mutations has already been reported in other European populations. Surprisingly, EGFR mutations rate was as high as 32% in African women patients (p&lt;0.001), whereas African men exhibited a very low frequency of EGFR mutations (5%, p&lt;0.001) as well as the French non immigrant patients (6%).
KRAS mutation rate was higher among white European (26%) than Asiatic (10%) or African (10%) patients. Although KRAS mutation rate did not differ by sex in white Europeans (men 25% versus women 27%, respectively), it was 3 fold more frequent in men than in women among African (19% versus 5%, respectively, p&lt;0.001) and Asiatic patients.Therefore EGFR or KRAS mutation rates in African immigrant population in France are closer to those observed in Asians or even Hispanics, than in Caucasians. These frequencies also differ from those reported in African Americans. The ancestral and recent migration of populations as well as social habits could explain these results.
Citation Format: Antoinette Lemoine, Raphael Saffroy, Nelly Bosselut, Emmanuel Lecorche, Reza Etessami, Marc A. Allard, Jean Tredaniel, Andre Balaton, Pierre Validire, Jean F. Morere. The prevalence of EGFR and KRAS mutations in a population of African immigrants in France is closer to that of Asian populations than to white Europeans. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2231. doi:10.1158/1538-7445.AM2014-2231
Abstract 2234: Combined analysis of TERT, EGFR and IDH status define distinct prognostic classes of GBM
Authors: Labussiere Marianne , Boisselier Blandine , Mokhtari Karima , Rahimian Anais , Saulnier Olivier , Marie Yannick , Sanson Marc 
Published: May 2015

Abstract
Background. The importance of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently strengthened by the frequent occurrence of TERT promoter mutations in glioblastomas.
Methods. We sequenced TERT promoter mutation in 395 glioblastomas DNA and confronted the results with histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosome 9 and 10, TP53 mutation), and overall survival (OS).
Results. TERT promoter mutations (TERTp-mut) were found in 299/395 glioblastomas (75.7%) and were associated with an older age (median 59.6 vs. 53.6 years p&lt;0.0001). TERTp-mut was an independent factor of poor prognosis (OS= 13.8 months vs. 18.4 months), in both IDH mutated (OS= 13.8 months vs. 37.6., p= 0.022) and IDH wild type (IDH-wt) GBM (OS= 13.7 vs. 17.5 months, p= 0.006). TERTp-mut was associated with IDH-wt and EGFR amplification (EGFR-amp) status. In TERTp-wt group, OS was twice longer in EGFR wt compared to EGFR-amp GBM (OS= 26.6 months vs. 13.3 months; p= 0.005). In the EGFR-wt group, TERTp-wt patients had a much better outcome (OS= 26.3 vs. 12.5 months; p&lt; 0.0001), whereas in the EGFR-amp group, TERTp-mut patients did better (OS = 15.8 vs. 13.3 months; p= 0.05). Taken together the absence of both EGFR-amp and Tertp-mut is associated with better survival (26.5 months for IDH-wt, 36.7 months for IDH-mut patients).
Conclusions. The analysis of TERT promoter mutations, in combination with EGFR amplification and IDH mutation status, refines the prognostic classification of GBM.
Citation Format: Marianne Labussiere, Blandine Boisselier, Karima Mokhtari, Anais Rahimian, Olivier Saulnier, Yannick Marie, Marc Sanson. Combined analysis of TERT, EGFR and IDH status define distinct prognostic classes of GBM. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2234. doi:10.1158/1538-7445.AM2014-2234
Abstract 2258: Tempol diet provides chemoprotection against UV-induced skin cancer in mice with epidermal Smad4 deletion
Authors: Mitra Doyel , Li Bian , Zhang Qinghong , Mitchell James B. , Wang Xiao-Jing 
Published: May 2015

Abstract
Solar ultraviolet (UV) radiation is the primary cause of skin cancer. Non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of skin cancer and accounts for 2-3 million worldwide cases of cancer each year. Smad4 loss occurs frequently in human skin squamous cell carcinoma (SCC), and we have shown that keratinocyte specific Smad4 deletion in K14.Smad4-/- mice leads to reduced expression of DNA repair genes, increased DNA damage and increased susceptibility to UV-induced SCC. Since UV-irradiation leads to oxidative damage to DNA, and unrepaired DNA damage may lead to cancer, so we tested if administration of an antioxidant, 4-hydroxy-tempo (tempol) in the diet of WT and K14.Smad4-/- mice reduces UV-induced skin carcinogenesis. In the present study, we divided WT and K14.Smad4-/- mice into two groups each, one group was fed tempol chow while the other group was fed control chow. All mice were exposed to chronic UV irradiation for 38 weeks from 3 months of age. Indeed, the tempol diet led to delayed onset and reduced number of skin tumors in K14.Smad4-/- mice. Tempol diet led to reduced 8-hydroxyguanosine staining, indicative of reduced oxidative DNA damage, as well as reduced cox-2 expression in the skin of K14.Smad4-/- mice compared to K14.Smad4-/- mice on control diet. It is plausible that reduced inflammation in these mice led to reduced carcinogenesis, these and other mechanisms are being investigated.
Citation Format: Doyel Mitra, Bian Li, Qinghong Zhang, James B. Mitchell, Xiao-Jing Wang. Tempol diet provides chemoprotection against UV-induced skin cancer in mice with epidermal Smad4 deletion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2258. doi:10.1158/1538-7445.AM2014-2258
Abstract 2262: Elevated peroxiredoxin expression in breast cancer and its protective role in doxorubicin-resistance
Authors: Muhlbauer Jillian , Perlmutter Gregg , McDonald Caitlin , Cintineo Harry , Aiello Caterina , Phelan Shelley A. 
Published: May 2015

Abstract
Peroxiredoxin (Prdx) proteins are thiol-specific antioxidants that protect cells from oxidative stress in various normal and disease states. There are six different Prdx proteins expressed in mammals, each possessing a characteristic tissue and subcellular distribution. Recent studies have revealed elevated Prdx levels in many cancers, suggesting a protective role for these proteins in cancer cell survival. In the present study we analyzed Prdx levels in several human breast tumor samples, and also investigated the function of Prdx proteins in the MCF-7 breast cancer cell line. Analysis of breast tumor and adjacent normal breast tissue from almost 20 patients showed elevated levels of most Prdx proteins in tumor tissue from the majority of patients. To address the role of Prdxs in breast cancer, we used transient siRNA transfections of MCF-7 cells and examined resulting cell viability in the absence and presence of doxorubicin treatment. Our data show that individual suppression of four of six of the Prdx proteins leads to increased cell death, as well as increased sensitivity to doxorubicin-induced toxicity. Finally, we show that clonal selection of doxorubicin-resistant MCF-7 cells by two-week culture in 0.1uM doxorubicin resulted in a marked elevation in the expression of several Prdx proteins. Similar studies are currently underway in the highly metastatic MDA cell line, and possible upstream regulators of Prdx overexpression in these lines are being investigated. Together, these data show a strong protective role for Peroxiredoxins in breast cancer cell survival, and suggest that Prdx overexpression in breast cancer may play a role in chemotherapy-resistance.
Citation Format: Jillian Muhlbauer, Gregg Perlmutter, Caitlin McDonald, Harry Cintineo, Caterina Aiello, Shelley A. Phelan. Elevated peroxiredoxin expression in breast cancer and its protective role in doxorubicin-resistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2262. doi:10.1158/1538-7445.AM2014-2262
Abstract 2282: Calmodulin binding to DR-5 and the role of CaM-DR-5 binding in DR-5-mediated DISC formation in breast cancer
Authors: Fancy Romone M. , Wang Hong , Zhou Tong , Song Yuhua 
Published: May 2015

Abstract
Molecular classification of breast cancers into receptor-based subtypes, including estrogen positive or triple negative breast cancers, establish targets that guide individualized treatment for patients (Journal of clinical oncology:27, 1153-1154, 2009). However, drug resistance observed for breast cancer raises the challegens for the breast cancer treatment (CA: a cancer journal for clinicians 59, 303-313, 2009). Targeting the death receptor-5 (DR-5) to induce breast cancer apoptosis is a promising strategy for breast cancer treatment (Immunity 3, 673-682, 1995, Breast Cancer Res Treat 113, 217-230, 2009). TRA-8 is a DR-5 specific agonistic antibody (Nature medicine 7, 954-960, 2001), and TRA-8 can induce apoptosis in breast cancer cells (Clinical cancer research: 9, 3731-3741, 2003). TRA-8 signal DR-5-mediated apoptotic signal via formation of the death inducing signaling complex (DISC) at the DR-5 death domain (Immunity 12, 599-609, 2000). Calmodulin (CaM) is a mediator of calcium signaling and has been shown to play a role in regulating DR-5 mediated apoptosis (Biochem Cell Biol 87, 919-926, 2009). Understanding the mechanism of DR-5-CaM interaction and the role of CaM-DR-5 binding in regulating DR-5 mediated DISC formation, may unveil CaM-DR-5 binding as a potential target to modulate DR-5 mediated apoptosis. In this study we characterize an interaction between CaM and DR-5 and the role of CaM-DR-5 binding in DR-5-mediated DISC formation in MCF-7 and MDA-MB-231 breast cancers. Complex-immunoprecipitation of DR-5 from MCF-7 and MDA-MB-231 lysates demonstrated endogenous CaM and DR-5 form a complex. Native PAGE of recombinant 6xHis-SUMO-CaM incubated with MCF-7 and MDA-MB-231 lysates showed the formation of a CaM and DR-5 complex. CaM pull down of DR-5 from MCF-7 and MDA-MB231 lysates in the presence of 1 mM Ca2+ or 2 mM EGTA showed CaM/DR-5 interaction is calcium dependent. TRA-8 activation of DR-5 resulted in CaM recruitment into the DR-5 mediated DISC. Additionally, Either EGTA or CaM antagonist trifluopherazine (TFP) attenuated DR-5 mediated DISC formation in MCF-7 and MDA-MB-231 breast cancers. We present evidence for the Ca2+ dependent CaM and DR-5 interaction and a role of CaM-DR-5 binding in regulating DR-5 mediated DISC formation in breast cancer cells. Results from this study provide the basis for the further characterization of CaM-DR5 interactions and its important role in cellular activities, which could lead to novel strategies for effectively regulating DR-5-mediated apoptosis in breast cancer.
Citation Format: Romone M. Fancy, Hong Wang, Tong Zhou, Yuhua Song. Calmodulin binding to DR-5 and the role of CaM-DR-5 binding in DR-5-mediated DISC formation in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2282. doi:10.1158/1538-7445.AM2014-2282
Abstract 2285: PKC activation sensitizes certain basal breast cancer cell lines to the Smac mimetic LBW242
Authors: Cornmark Louise , Holmgren Christian , Masoumi Katarzyna , Larsson Christer 
Published: May 2015

Abstract
There is a need for novel strategies to initiate cancer cell death. One approach is the use of Smac mimetics, such as LBW242, which antagonize inhibitor of apoptosis proteins (IAP)s and facilitates cell death. Recent studies have shown that combinations of Smac mimetics and chemotherapeutic agents increase cancer cell death. Here we show that the protein kinase C (PKC) activator TPA together with LBW242 induce cell death in two basal breast cancer cell lines (MDA-MB-468 and BT549), that are resistant to LBW242 as a single agent. Eleven other LBW242-insensitive cancer cell lines were not influenced by the TPA+LBW242 combination. The TPA+LBW242 effect was suppressed by the PKC inhibitor GF109203X, indicating dependence on PKC enzymatic activity. The PKC effect was mediated via increased synthesis and release of TNFα which can induce death in the presence of LBW242. The cell death, coinciding with caspsae-3 cleavage, was suppressed by caspase inhibition and preceded by the association of RIP1 with Caspase-8, as seen in complex II mediated apoptosis. Our data suggest that in certain basal breast cancer cell lines co-treatment of TPA with LBW242 induces cell death highlighting the potential of using these pathways as molecular targets for basal-like breast cancers.
Citation Format: Louise Cornmark, Christian Holmgren, Katarzyna Masoumi, Christer Larsson. PKC activation sensitizes certain basal breast cancer cell lines to the Smac mimetic LBW242. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2285. doi:10.1158/1538-7445.AM2014-2285
Abstract 2287: Nuclear localization of N-myc downstream regulated gene 4: A novel therapeutic target in meningioma
Authors: Kotipatruni Rama P. , Ren Xuan , Vanderwaal Robert P. , Thotala Dinesh , Jaboin Jerry J. 
Published: May 2015

Abstract
NDRG4 is a member of the N-Myc downregulated gene family (NDRG) belonging to the alpha/beta hydrolase super family. The roles of NDRG4 in meningioma tumor development have not previously been evaluated. Effective local therapies include surgery and radiation, but there is a need for novel molecular targets to improve survival and reduce morbidity for meningioma patients. We have recently identified the N-Myc down regulated gene 4, NDRG4, protein as being overexpressed in aggressive meningiomas and demonstrated that NDRG4 downregulation results in decreased cell viability, migration and invasive properties. NDRG4 was initially identified as a cytoplasmic protein. In the present study, we proposed that nuclear localization of NDRG4 and the role of NDRG4 in cell proliferation. Subcellular distribution of NDRG4 was identified by western blotting in nuclear and cytosolic extracts. Immunocytofluoresence analysis revealed the NDRG4 nuclear localization. Here we demonstrate that depletion of NDRG4 induces the predominant form of cell death is apoptosis, utilizing DNA laddering and Annexin V/APC flow cytometry assay. We show that apoptosis caused by transduction of lentiviral shNDRG4 involves of p53 phoshorylation at ser 15, Bax activation. Flow cytometry analysis revealed changes in mitochondrial membrane potential (Ψm), which was observed by JC-1. Sub-cellular distribution of Bax and Cytochrome c indicated the mitochondrial-mediated apoptosis. In conclusion, we show that NDRG4 is also a nuclear protein expressed in response to cell proliferation and demonstrated the suppression of NDRG4 induces the apoptosis through p53 and Bax mediated intrinsic apoptotic pathway.
Citation Format: Rama P. Kotipatruni, Xuan Ren, Robert P. Vanderwaal, Dinesh Thotala, Jerry J. Jaboin. Nuclear localization of N-myc downstream regulated gene 4: A novel therapeutic target in meningioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2287. doi:10.1158/1538-7445.AM2014-2287