bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 112: Concurrent analysis between copy number variation and gene expression of non-smoking lung cancer females in Taiwan
Authors: Chang Jung-Chih , Lu Tzu-Pin , Chen Pei-Chun , Lee Jang-Ming , Hsu Chung-Ping , Tsai Mong-Hsun , Chuang Eric Y. , Lai Liang-Chuan , Hsiao Chuhsing K. 
Published: February 2011

Abstract
Although smoking has been proved to be an important factor for lung cancer, the etiology and molecular mechanisms of non-smoking female lung cancer remain unclear. We collected paired normal and tumor lung tissues from 44 female non-smoking lung cancer patients. Copy number variation and Gene expression profiles were analyzed by Affymetrix U133plus 2.0 expression arrays and Affymetrix SNP 6.0 single nucleotide polymorphism (SNP) arrays. The data from two platforms were integrated for concurrent analyses in order to elucidate the putative molecular mechanisms. We first identified the probes located at the same region of gene expression and copy number variation (CNV). Next, we calculated the Pearson correlation coefficient to assess the association between log intensity values of mRNA expression and the corresponding averaged intensity values of SNP probes in both tumor and normal tissues. Genes were then selected based on the following two criteria: (1) the difference in expression-SNP correlations between normal and tumor tissues &gt; 0.7, and (2) the absolute expression-SNP correlation of either normal or tumor &gt;0.3. The selected genes were further analyzed by Ingenuity Pathway Analysis (IPA) to explore the related pathways and networks. Results of IPA showed that mitochondrial dysfunction, IGF-1 signaling, and cell cycle: G1/S checkpoint regulation pathways were significantly dysregulated in tumor tissues. The associations between lung cancer and genomic alternations in these enriched pathways have been reported previously, such as overexpression of IGF1R in IGF-1 signaling pathway might resist EGFR inhibitors used in lung cancer treatment. In summary, with the integrated data of copy number variation and expression, the concurrent analyses help to dissect lung carcinogenesis of non-smoking lung cancer females in Taiwan.
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 112.
Abstract 1120: Low prevalence of TP53 mutations in pediatric rhabdomyosarcoma
Authors: Ognjanovic Simona , Martel-Planche Ghyslaine , Olivier Magali , Hainaut Pierre 
Published: February 2011

Abstract
The tumor suppressor gene TP53 is the most commonly mutated gene in human cancer. Mutations in TP53 in rhabdomyosarcoma (RMS) have been associated with aggressive tumors and poor prognosis, however, reported prevalence of mutations in these tumors varied with smaller series reporting larger prevalence. Apart from gene mutations, p53 function can also be attenuated by overexpression of MDM2. Most recent report suggested extremely low prevalence of TP53 mutations and MDM2 amplifications (Taylor et al., 2000). We had 40 embryonal and 40 alveolar RMS tumor samples available for TP53 mutations/MDM2 amplification analyses, the largest series analyzed thus far.
Half of the available samples were histopathology slides and the other half were frozen tumor tissue. The average age of slides was 13 years, therefore only 24 out of 40 slide DNA samples were of sufficient quality/quantity to complete direct sequencing of TP53 exons 4-9, limiting our results to 64 samples. MDM2 amplification was analyzed by differential PCR using dopamine gene as control. TP53 sequencing detected only one single mutation, p. D259Y, and six polymorphisms (Table 1).Table 1.Mutations and polymorphisms in TP53 gene in 64 pediatric embryonal and alveolar RMS. DiagnosisAgeGenderRacePrimary siteStageGene Variation*Protein ChangeMutationsERMS1MWhiteRight thighN/Ag.13412G&gt;Tp. D259YPolymorphismsERMS0MBlackRight ankleN/Ag.14077T&gt;CN/A ERMS4FBlackBladder2g.12708A&gt;Gp. R213R ARMS4MAsianButtockN/Ag.12708A&gt;Gp. R213R ARMS6MWhiteForearmN/Ag.12708A&gt;Gp. R213R ERMS6FWhiteUterusN/Ag.12708A&gt;Gp. R213R ARMS9FWhiteParotid mass1g.11370C&gt;Tp. P47S* nucleotide number based on GenBank sequence NC_000017.9
No distinct pattern between TP53 mutation/polymorphisms was associated with any RMS subtype. Likewise, no MDM2 amplifications were observed.
In conclusion, we confirm the extremely low prevalence of TP53 mutations/MDM2 amplifications in pediatric RMS (1.25% and 0% respectively). The possible inactivation of p53 function by other mechanisms thus remains to be elucidated.
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 1120.
Abstract 1122: UVB-induced PTEN down-regulation and its association with skin carcinogenesis
Authors: Ming Mei , Han Weinong , Shea Christopher R. , Soltani Keyoumars , Maddox Jessica , Freeman Diane M. , He Yu-Ying 
Published: February 2011

Abstract
Non-melanoma skin cancer including squamous cell carcinoma (SCC) is the most common cancer in the United States and ultraviolet (UV) radiation in sunlight is a major environmental trigger for skin carcinogenesis. PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a proven critical tumor suppressor. We found that UVB down-regulates PTEN in primary human keratinocytes, human HaCaT keratinocytes and mouse skin, and the ERK/AKT/PTEN axis may form a positive feedback loop following UVB irradiation. We also examined PTEN levels in different types of skin cancer that are associated with chronic sun exposure, including actinic keratoses (AK, premalignant lesion), keratocanthoma (KA), squamous cell carcinoma (SCC) in situ (SCC is), SCC invasive (SCC iv). As compared with normal skin, PTEN expression is significantly down-regulated in human skin cancer with these different diagnoses. In addition, PTEN down-regulation is significantly associated with solar UV damage and age of patients. Our findings indicate that UVB radiation suppresses PTEN expression in human skin cancer and this down-regulation may play critical roles in the development and progression of human skin cancer.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1122.
Abstract 1123: PTEN loss increases efficiency of breast tumor metastasis
Authors: Vitolo Michele I. , Thompson Keyata , Whipple-Bettes Rebecca A. , Matrone Michael A. , Yoon Jennifer R. , Balzer Eric M. , Cho Edward H. , Martin Stuart S. 
Published: February 2011

Abstract
Breast cancer is the most frequent malignancy in women, and although many breast cancers are curable via surgery, approximately one quarter maintain a latent and insidious characteristic of slow growth with early metastasis. The loss of the tumor suppressor PTEN has been associated with breast cancer stage, lymph node status, and disease-related death, and the high rate of loss in primary tumors suggests a potential role in initiation and/or progression of the disease. However, specific cellular alterations in human breast epithelium controlled by PTEN inactivation, which lead to an increased metastatic phenotype, remain poorly defined. We have determined that heterozygous and homozygous loss of PTEN in non-tumorigenic mammary epithelial cells (MECs) was insufficient to promote anchorage-independent growth. However, MECs with PTEN loss maintained elevated activation of the PI3K/Akt and MAPK pathways and apoptotic resistance to cell rounding and matrix detatchment. We have also recently determined that PTEN expression loss leads to the production of long, dynamic, tubulin-based membrane protrusions upon detachment, which are increased in frequency, number and length per cell as compared to their isogenic, PTEN-expressing parental counterparts. These novel structures, termed microtentacles (McTNs), are structurally distinct from classical actin-based extensions of adherent cells, persist for days in breast tumor lines that are resistant to anoikis, and aid in the reattachment to matrix or cell monolayers. Therefore, the combination of apoptotic resistance and enhanced McTN formation due to PTEN loss may have important consequences for facilitating tumor cell extravasation and efficient adherence in metastatic sites.
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 1123.
Abstract 1124: Characterization of a PTEN C2 loop mutation in a human breast cancer cell line
Authors: Chan Andrew M. , Singh Gobind , Odriozola Leticia , Kennedy Colin 
Published: February 2011

Abstract
PTEN is a major tumor suppressor gene inactivated in over 30% of human cancer. It encodes a lipid phosphatase with specificity towards phosphatidylinositol (3,4,5) triphosphate (PIP3). PTEN phosphatase activity is crucial to its ability to control cell size, proliferation, motility and survival. The role of PTEN in human breast cancer is well-established. Although the frequency of PTEN mutation in human breast cancer is low (5-10%), a significant fraction of advanced breast cancer has reduced PTEN expression. Furthermore, germ line mutation in PTEN gene constitutes the genetic basis of Cowden's Disease (CD) Syndrome. CD is a harmatoma syndrome with patients displaying aberrant overgrowth of multiple tissue types. Individuals are at a greater risk of developing malignancy of the breast, colon, skin and thyroid.
Our laboratory has identified a unique mutation in the C2 loop of PTEN from a human metastatic breast carcinoma cell line, MDA-MB-453. A G to A change substitutes the glutamate (GAG) at codon 307 (E307) to a lysine (AAA). The PTEN C2 loop (aa282-312) is a region on the cytosolic side of the C2 membrane-binding domain. Mono-ubiquitination at K289 within the C2 loop has been shown to promote nuclear translocation. More importantly, unlike the wild-type protein, the E307K mutant is almost undetectable in the nuclear compartment of MDA-MB-453. Biochemically, PTEN E307K mutant displayed similar phosphatase activity towards soluble lipid substrates. More importantly, PTEN E307K displays a striking ability to form an affinity complex with the p53 tumor suppressor. Consistent with this finding, the expression of E307K exerts chemoprotective effect against cisplatinum induced cell death.
Based on this preliminary data, we hypothesize that the negatively-charged glutamate residues of PTEN C2 loop play regulatory roles in nuclear translocation and p53-binding. Mutating those residues to lysine creates cryptic ubiquitination sites that subvert the natural ubiquitination at K289, and thus impedes nuclear translocation.
Funding: DOD - DAMD17-03-1-0682 (AMC); NCI - RO1CA095063 (AMC), T32CA078207 (GS); Midwest Athletes against Childhood Cancer (AMC); Advancing Healthy Wisconsin Funds (AMC)
Acknowledgement: Dr. Xuejun Jiang (Memorial Sloan Kettering Cancer Center, NY) and Dr. Zhen-Qiang Pan (Mount Sinai School of Medicine, NY) for providing the NEDD4-1 and ubiquitination reagents
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 1124.
Abstract 1127: Dysregulation of tumor suppress gene LKB1 in pancreatic cancer
Authors: Wei Chongjuan , Zhang Nianxiang , Liu Qian , Amos Christopher , Frazier Marsha 
Published: February 2011

Abstract
Pancreatic cancer is the fourth leading causes of cancer-related death in USA and the most common seen neoplsams in Peutz-Jeghers syndrome (PJS). PJS is an autosomal dominant disorder characterized by gastrointestinal hamartoma and predisposition to cancer. Patients with PJS have a 100-fold higher risk for development of pancreatic cancer than the general population. Tumor suppressor LKB1 is the causative gene for PJS. LKB1 mutations have also been observed in a significant proportion of sporadic pancreatic cancer, suggesting a role for LKB1 in pancreatic cancer although the underlying mechanism has not been elucidated yet. To evaluate the role of LKB1 in pancreatic tumorigenesis, we extracted RNA from our unique collection of fifty-three tumor/normal pairs of snap frozen pancreatic cancer and adjacent normal tissue from the same patient. RT-PCR results showed that LKB1 is downregulated in ∼74% of the cancer tissue compared to adjacent normal pair, and in ∼40% of pairs the downregaulation is greater than 2 folds. To confirm our result, we analyzed the publically available gene expression microarray data on 36 pancreatic cancer samples and 12 normal controls. We observed downregulation of LKB1 in these data and the difference in LKB1 expression levels in pancreatic cancer vs normal was statistically significant (p=0.0003). LKB1 has been reported to negatively regulate mTOR signaling. Therefore, we further analyzed whether there was correlation between the expression of LKB1 and key protein in mTOR signaling pathway. Our results showed that the expression of LKB1 is inversely correlated with that of EIF4A and EIF4E, which are translation initiation factors. These findings suggest that dysregulation of LKB1 and its downstream signaling pathway may play an important role in pancreatic tumorigenesis.
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 1127.
Abstract 1136: Detection and characterization of circulating tumor cells in localized and metastatic prostate cancer patients using CTC-Chip microfluidic technology
Authors: Nagrath Sunitha , Stott Shannon L. , Lee Richard J. , Yu Min , Ulkus Lindsey L. , Iafrate John A. , Smith Mathew R. , Tompkins Ronald G. , Sequist Lecia V. , Haber Daniel A. , Maheswaran Shyamala , Toner Mehmet 
Published: February 2011

Abstract
Despite recent molecular advances, the treatment of localized and metastatic prostate cancer has changed little in recent decades and it remains a major cause of cancer deaths in men. Localized prostate cancer may be either indolent or invasive, without reliable distinguishing markers, and the absence of tumor tissue from patients with metastatic bone disease has hampered understanding of acquired resistance to primary hormonal therapy. Given the predominant hematogenous spread of prostate cancer, circulating tumor cells (CTCs) may provide an indicator of vascular invasiveness, as well as a source of tumor specimens for molecular analysis, but available technologies have been limited by relatively low sensitivity. Huge strides in engineering at smaller scales have lead to the tremendous progress in microfabricated devices to facilitate both applied and basic research. Applying a multi-disciplinary approach, we have developed a microfluidic technology “CTC-Chip” for diagnosis and monitoring of non-hematological cancers. Using the CTC-Chip, we were able to isolate CTCs in patients with both localized and metastatic prostate cancer. In patients with advanced cancer, CTCs were present at a frequency of 34 CTCs/mL (range 14-653), with a profound decline in numbers during response to hormone withdrawal therapy. Molecular markers, including the characteristic TMPRSS2-ERG translocation, are readily identified in CTCs. In patients with early stage, resectable prostate cancer, we have monitored CTC load in circulation following surgical resection of the primary tumor. CTCs were examined the day following surgical resection, at postoperative day 9, and at greater than 3 months, coincident with scheduled postoperative clinical visits. Longitudinal monitoring of CTCs revealed all CTC-positive cases showed disappearance of CTCs following prostate resection, with some having an immediate decline and others having a delayed (&gt;24 hours) response. No evident differences in tumor pathology or operative procedure distinguished patients with a rapid versus delayed postoperative CTC decline. Dual staining of captured CTCs for PSA and Ki67 indicated a broad range in proliferative index of CTCs among patients with different clinical courses. Thus, the quantitative isolation and analysis of CTCs in both localized and metastatic prostate cancer provides novel insights into early hematogenous dissemination and enables molecular analyses of treatment-responsive and -resistant disease.
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 1136.
Abstract 1139: Complete characterization of prostate cancer genomes by massively parallel sequencing
Authors: Berger Michael F. , Lawrence Michael S. , Cibulskis Kristian , Pflueger Dorothee , Demichelis Francesca , Sougnez Carrie , Onofrio Robert C. , Ambrogio Lauren , Fennell Timothy , Parkin Melissa , Carter Scott L. , Saksena Gordon , Sivachenko Andrey , Voet Douglas , Wilkinson Jane , Fisher Sheila , Winckler Wendy , Ardlie Kristin , Chant John , Baldwin Jennifer , Gerstein Mark , Golub Todd R. , Meyerson Matthew , Tewari Ashutosh K. , Gabriel Stacey B. , Lander Eric S. , Getz Gad , Rubin Mark A. , Garraway Levi A. 
Published: February 2011

Abstract
Prostate cancer is the most common type of cancer diagnosed among men in the United States, accounting for 200,000 new cases and 27,000 deaths per year. Prior genetic studies have shown that chromosomal rearrangements comprise a major mechanism of oncogene activation in prostate cancer. For example, androgen-regulated gene fusions involving ETS family transcription factors are present in the majority of prostate cancers, yet the full repertoire of genomic alterations driving prostate carcinogenesis and progression remains unknown. Toward this end, recent technological advances have made it possible to characterize the full complement of somatic mutations in a single tumor through whole genome sequencing.
We are using massively parallel sequencing technology to characterize the complete genomes of several primary prostate adenocarcinomas at &gt;30x coverage. All samples are high-grade primary tumors (Gleason grade 7 to 9) and include cases with and without known ETS family translocations. For each tumor, we are also obtaining &gt;30x sequence coverage of matched normal DNA from blood of these same patients in order to determine the somatic component of the overall variation we observe. Our results indicate that translocations and other chromosomal rearrangements occur frequently in prostate cancer, at a rate of &gt;100 per genome. Further, we have discovered many nonsynonymous sequence mutations (point mutations and indels) in each tumor, some of which may represent novel candidate drivers of tumor progression. The overall rate of somatic point mutations is approximately 1 per Megabase. Integrated analysis of all genomes reveals both recurrent and private alterations. Together, these results illuminate potential avenues for target discovery and demonstrate the unparalleled value in performing complete genome sequencing in this malignancy.
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 1139.
Abstract 1142: Development and validation of a multiplexed PCR-coupled liquid bead array for gene expression in circulating tumor cells
Authors: Markou Athina N. , Strati Areti D. , Malamos Nikolaos , Georgoulias Vasileios , Lianidou Evi S. 
Published: February 2011

Abstract
INTRODUCTION: The aim of our study was to develop and validate a multiplexed PCR-coupled liquid bead array to detect the expression of multiple genes in Circulating Tumor Cells (CTCs), and application of this assay in peripheral blood samples of breast cancer patients.
PATIENTS AND METHODS: We designed a novel multiplexed PCR-coupled liquid bead array that consist of the following steps: a) in silico designed gene-specific primers and capture probes for CK-19, HER-2, Mammaglobin (hMAM), MAGE-A3, TWIST-1 and PBGD (as a control gene), b) RNA isolation from immunomagnetically enriched CTCs, c) multiplex PCR, d) sequence hybridization array, e) detection in the Luminex platform. We performed extensive optimization experiments using the SKBR3 and MDA-MB-231 cell lines as positive controls, to maximize analytical sensitivity and specificity and we further validated the performance of this array in respect to cross reactivity and intra and inter-precision. Finally, we applied the developed methodology in peripheral blood samples of 37 patients with operable breast cancer, 25 patients with verified metastasis and 17 healthy individuals.
RESULTS: The analytical performance of the developed array was evaluated in tumor cell lines in respect to analytical sensitivity and specificity. Cross reaction studies were performed for each gene target in the presence of all other targets. The assay is highly specific for each gene in complex multiplexed formats, since the discriminatory power of fluorescent bead sets is unique to specifically detect by sequence hybridization the presence of individual gene specific PCR products. The developed liquid bead-based array is highly sensitive, since it can detect the expression of each individual gene at one SKBR3 cell level. The validation of the array included within day and between-days precision studies. None of the genes tested was detected in the CTC fraction of healthy donors while in patients with verified metastasis, CK-19 was detected in 45%, HER-2 in 20%, MAGE-A3 in 30%, hMAM in 15% and TWIST-1 in 20%. In operable breast cancer patients, CK-19 was detected in 13.5%, HER-2 in 5%, TWIST-1 in 16.2%, MAGE-A3 in 37.8% while hMAM was not detected in any sample.
CONCLUSIONS: Our results show that individual gene expression can be readily measured in CTCs using a bead-based platform. This may form an efficient basis for a multiplex approach to measure multiple genes (up to 100) in the same sample, thus saving sample volume and reducing the total cost and time of analysis. This is the first time that the Luminex technology is used for gene expression studies in CTCs.
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 1142.