bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2202: Identification of CDH1 mutations in patients with lobular carcinoma with and without a family history of gastric cancer
Authors: Valente Allyson L. , Ellsworth Rachel E. , Lubert Susan , Holliday Charvonne , Shriver Craig D. 
Published: June 2012

Abstract
Background: The E-cadherin (CDH1) gene is involved in cell adhesion and maintenance of tissue architecture. Loss of expression of CDH1 has been found in both invasive lobular carcinoma (ILCA) of the breast as well as hereditary diffuse gastric cancer (HDGC). While mutations in CDH1 have been found in patients with hereditary diffuse gastric cancer, less is known about the role of CDH1 mutations in patients with breast cancer, thus mutation status was determined in a breast cancer cohort with and without family histories of gastric cancer.
Methods: The Clinical Breast Care Project database was queried to identify all patients with ILCA with or without a family history of gastric or stomach cancer as well as those with non-lobular invasive cancer with a family history of gastric or stomach cancer. Genomic DNA was isolated from peripheral blood samples. DNA variants were detected for each exon using high-resolution melting technology and the underlying change identified by direct sequencing.
Results: Of the 72 patients with ILCA, five had a first degree relative with stomach cancer; 14 patients with non-lobular invasive cancer (12 IDCA, one mixed lobular and ductal, and one tubular) had first degree relatives with stomach or gastric cancer. Three mutations previously associated with gastric cancer were identified: A617T and V832M were identified in a patient with ILCA with no history of gastric cancer and in a patient with IDCA with a family history of gastric cancer, respectively, while one patient with ILCA and no family history harbored the splice site mutation 1137G-T. Three novel variants were also identified: G879S, in a patient with ILCA and no family history, P825Q in a patient with mixed lobular and ductal features with a family history of stomach cancer and L230F in a patient with IDCA and a family history of stomach cancer.
Conclusions: The frequency of CDH1 mutations in this patient population was low (∼7%) and were split between patients with ILCA and no family history of gastric cancer and those with non-lobular cancers and at least one family member with gastric or stomach cancer. Identification of known mutations in patients with non-lobular carcinomas suggests that while these specific CDH1 mutations are associated with increased risk of hereditary diffuse gastric cancer, they do not confer increased risk for lobular cancer. In those patients with ILCA, the low frequency of germline mutations in CDH1 suggests alternate methods, such as epigenetic modification or miRNA silencing, may be driving the suppression of expression of E-cadherin and the development of ILCA.
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 2202. doi:10.1158/1538-7445.AM2011-2202
Abstract 2204: Loss of heterozygosity in ameloblastic odontogenic tumors
Authors: Gomes Carolina C. , Galvão Calrice F. , Diniz Marina G. , De Marco Luiz , Macedo Paula S. , Vargas Pablo A. , Taylor Adalberto M. , Gomez Ricardo S. 
Published: June 2012

Abstract
The interrelationship of the odontogenic lesions consisting of odontogenic epithelium with odontogenic ectomesenchyme has not been established. To give further insight into the molecular pathogenesis of these odontogenic tumors, the present study investigated allelic loss of a panel of tumor suppressor genes. Six samples of ameloblastic fibroma (AF), 3 cases of ameloblastic fibro-odontoma (AFO) and 3 ameloblastic fibrosarcomas (AFS) were included in the study. We observed loss of heterozygosity (LOH) in 2/6 samples of AF in at least one of the analyzed markers and loss in all the three samples of AFO and AFS in more than one marker. Results are shown in table 1. For the markers AFM238WF2(CHRNB1) and P53, LOH was found all the three types of lesion studied. However, the markers D3S1293, D9S157 and D9S171 showed LOH only in AFS and none of the samples included in the study showed LOH of D11S1369 and D3S1029 markers. LOH was observed for the marker D9S162 in only one sample of AFO. Our data show that AFS have distinct patterns of LOH in tumor suppressor genes compared to their benign counterparts and allelic loss of some markers may be related to tumor behavior, as AFS is a malignant odontogenic tumor and the others are benign entities.
This study was supported by FAPEMIG and CAPES, Brazil.
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 2204. doi:10.1158/1538-7445.AM2011-2204
Abstract 2205: Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas
Authors: Yoon Jung Hwan , Song Jae Hwi , Choi Yoo Jin , Park Won Sang 
Published: June 2012

Abstract
Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. The aim of this study is to determine whether inactivation of the GKN1 gene is involved in the development and/or progression of the gastric cancers. GKN1 expression was examined in gastric adenomas and cancer by immunohistochemistry and Western blot analysis. We also analyzed mutation and epigenetic alteration, DNA copy number change and mRNA transcript of GKN1 in gastric adenomas and carcinomas. The effect of GKN1 on cell proliferation and death was further examined in wild-type GKN1 transfected AGS gastric cancer cells. In immunohistochemistry, reduced or loss of GKN1 expression was detected in 36 (90%) and 170 (89.5%) of 40 adenomas and 190 gastric cancers, respectively. Statistically, there was no significant relationship between altered expression of GKN1 protein and clinicopathologic parameters, including depth of invasion, location, and lymph node metastasis (Chi-Square test, P&gt;0.05). In Western blot analysis, absence or reduced expression was found in 21 (84.0%) of 25 gastric carcinomas. No mutation was detected in gastric tumors, and hypermethylation of GKN1 gene was found in 2 gastric cancers. Interestingly, DNA copy number and mRNA transcript of GKN1 were significantly decreased in gastric cancers. In functional analysis, AGS gastric cancer cells transfected with GKN1 wild-type showed marked inhibition of cell proliferation and induction of cell death. These data suggest that inactivation of the GKN1 gene may play an important role in the development of sporadic gastric cancers, as an early event.
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 2205. doi:10.1158/1538-7445.AM2011-2205
Abstract 2232: Effectiveness evaluation of an in vitro nucleic acid amplification test for quantification of BCR-ABL fusion transcript variants in human whole blood
Authors: Stanoszek Lauren , Blomquist Thomas , Crawford Erin L. , Austermiller Bradly , Spitzer Casey , Willey Paige FS , Willey James C. 
Published: June 2012

Abstract
Quantitative measurement of BCR-ABL fusion gene transcripts in whole blood by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) is a clinically validated method to monitor tyrosine kinase inhibitor drug response in patients diagnosed with chronic myelogenous leukemia (CML). Monitoring of BCR-ABL expression in blood of cML patients under treatment with a tyrosine kinase inhibitor of BCR-ABL is considered standard of care. A three log or greater reduction in BCR-ABL expression from baseline is considered a Maximum Molecular Response (MMR). A subsequent 0.5 log increase in BCR-ABL from MMR is considered a sign of treatment failure sufficient to trigger change in treatment. The challenge is to develop a test with sufficient analytical performance characteristics and quality control to reliably measure BCRABL in MMR samples in which there may be less than 10 molecules in 300 of RNA extracted from whole blood. A method validation protocol was developed using the International Committee on Harmonization (ICH) Q2(R1) international validation guidelines. BCRABL variants b2a2 and b3a2 as well as the housekeeping gene GUSB were measured in KCL22 cell line RNA and Stratagene Universal Human Reference RNA test articles in extreme linear dilution assay, robustness testing conditions, and in multiple laboratories. Quality controls were developed to enable loading as much whole blood RNA into the assay as possible without assay interference. These included a reverse transcription (RT) standardization mixture comprising External RNA Control Consortium (ERCC) reagents to control for RT interference, and controls for genomic DNA contamination, RNA integrity, and PCR interference. Results: This test for b2a2 and b3a2 variants of BCR-ABL meets ICHQ2(R1) guidelines for specificity, linearity, accuracy, LOD and LOQ, imprecision, robustness, and reproducibility. Each analyte comprised by the test was linear (R2 &gt; 0.97) over more than 3 logs10, and demonstrated inter-experimental and inter-laboratory imprecision low enough to enable measurement of a 3-fold difference as significant (P &lt;0.05) from a value as low as five molecules/assay. Experiments are underway to quantify the amount of whole blood RNA that can be loaded into RT reaction without interference.
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 2232. doi:10.1158/1538-7445.AM2011-2232
Abstract 2244: The M-SKIP Project: an international pooled-analysis on melanocortin-1 receptor (MC1 R) variants and skin carcinogenesis
Authors: Gandini Sara , di Pietro Alessandra , Maisonneuve Patrick , Autier Philippe , Fargnoli Maria Concetta , García-Borrón José C. , Han Jiali , Kanetsky Peter A. , Landi Maria Teresa , Little Julian , Newton-Bishop Julia , Sera Francesco , Raimondi Sara 
Published: June 2012

Abstract
Background: MC1R is one of the major genes involved in the determinism of skin pigmentation. The role of MC1R variants in skin carcinogenesis was previously investigated by a meta-analysis of 18 published studies. Although the results were informative, published data were not enough to deeply investigate the specific contribution of each MC1R variant on skin cancer development.
Aim: The M-SKIP Project aims to perform an international collaborative pooled-analysis on the role of MC1R variants in skin carcinogenesis, using individual patient data. The main endpoint is skin cancer. Secondary endpoints are phenotypic characteristics involved in skin carcinogenesis, e.g. freckling.
Methods and Patients: An Advisory Committee of investigators with great expertise in melanoma and genetic research was established. The authors of appropriate papers were invited to provide their original published and unpublished data.
Preliminary results: Up to February 2010, 27 out of 35 contacted investigators (77%) agreed to join the M-SKIP Project. Thanks to the positive response obtained up to now, we estimate to receive data on around 6,500 melanoma cases, 1,500 non-melanoma skin cancer cases and 13,000 controls. So far, we have already received data on 2,683 melanoma cases, 1,364 non-melanoma skin cancer cases and 4,340 controls from 15 investigators internationally. After quality controls, data are inserted in a central database, and pooled-analysis will be performed in order to evaluate: (1) the association between MC1R variants and skin cancer overall, and by skin cancer type; (2) the association between MC1R variants and phenotypic characteristics under study; (3) MC1R-phenotype interaction in skin cancer risk. In addition, stratified analysis will be performed to understand the independent and dependent role of MC1R variants in skin cancer development by phenotypic characteristics.
Conclusion: The pooled analysis approach applied in such a setting is particularly useful because it will help reaching firm conclusions even in sub-group and interaction analyses, controlling for important confounders.
This data-bank will represent a reference and guide for all investigators working in this research field. Collaboration within investigators would significantly improve the knowledge and accelerate our understanding of the role of MC1R variants in skin carcinogenesis.
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 2244. doi:10.1158/1538-7445.AM2011-2244
Abstract 2254: Nuclear and cytoplasmic epidermal growth factor receptor and p16 expression as prognostic biomarkers in head and neck squamous cell carcinoma
Authors: Husain Hatim , Psyrri Amanda , Slebos Robbert , Ross Douglas T. , Burtness Barbara , Chung Christine H. 
Published: June 2012

Abstract
Introduction: Epidermal growth factor receptor (EGFR) and p16 staining have demonstrated to be strong prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). Patients with higher expression of EGFR in their tumors have been correlated with decreased survival and shorter time to recurrence. Patients with p16-positive (+) tumors [a surrogate marker of human papillomavirus (HPV) infection] have improved survival compared to p16-negative (−) tumors. We examined the interaction between the expression levels of total EGFR and p16 status, and further examined the association between nuclear EGFR and p16 status based on evidence that nuclear EGFR may have a distinct role in DNA damage repair and may function as a transcription factor.
Methods: A tissue microarray (TMA) containing 123 cores obtained from 101 HNSCC tumors was analyzed for EGFR expression (clone H11; DAKO, Carpinteria, CA) using an automated quantitative analysis (AQUA), and for p16 expression (clone E6H4; MTM Laboratories Inc., Westbrough, MA) using immunohistochemical (IHC) staining. Duplicate cores from a patient were averaged for analyses. The EGFR and p16 data were correlated with clinical data including demographics, primary subsite, disease stage, and survival.
Results: The total and nuclear EGFR data could be reliably obtained from 80 of 101 patients. The p16 data could be obtained from 87 of 101 patients [p16 (+), n=29; p16 (−), n=58]. The p16 staining was strongly associated with the oropharyngeal subsite (Chi2, p=&lt;0.0001) and poorly differentiated histology (Cochran-Armitage Trend Test, p=0.01). The expression of total and nuclear EGFR was higher in p16 (−) tumors compared to p16 (+) tumors (Wilcoxon Rank Test, p=0.038 and p=0.014, respectively). Interestingly, the higher expression of non-nuclear EGFR (combined cytoplasmic and membranous) staining did not associate significantly with p16 (−) tumors. Statistically significant differences in recurrence-free survival or overall survival were not detectable based on the EGFR and p16 expression, likely due to the small sample size and heterogeneity in the patient population.
Conclusions: The total and nuclear EGFR expression levels were higher in p16 (−) tumors compared to p16 (+); this may relate to recurrence and poor survival. Additionally, localization of EGFR may be a significant factor in its association with clinical outcomes. Further studies are indicated to determine the mechanistic link between these two prognostic factors and define the significance of EGFR localization to nucleus upon activation of the pathway.
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 2254. doi:10.1158/1538-7445.AM2011-2254
Abstract 2285: Stat3 modulates heregulin (HRG)-induced progesterone receptor (PR) transcriptional activation
Authors: Proietti Cecilia J. , Izzo Franco , Flaqué María Celeste Díaz , Vicario Rocío , Tkach Mercedes , Rivas Martín A. , Charreau Eduardo H. , Schillaci Roxana , Elizalde Patricia V. 
Published: June 2012

Abstract
The signal transducer and activator of transcription (Stat) family of proteins was found to be involved in crosstalks with both steroid hormones and type I receptor tyrosine kinases (RTKs) signaling pathways. We have previously demonstrated that HRG, a ligand of RTKs, transactivates PR both in C4HD cells from an experimental model of hormonal carcinogenesis in which MPA induced mammary adenocarcinomas in Balb/c mice, and in the human breast cancer cell line T47D (Mol Cell Biol. 2003 Feb;23(3):1095-111). We have also shown that HRG induces Stat3 tyrosine phosphorylation and transcriptional activation by a mechanism that requires PR signaling (Mol Cell Biol. 2009 Mar;29(5):1249-65).
In the present work we explored whether Stat3 acting as a coactivator, could modulate ligand-independent activation of PR by HRG. Assessment of the expression of the progestin-regulated gene bcl-X showed that HRG treatment of C4HD cells resulted in an increase in bcl-X protein levels. This effect was completely abolished when Stat3 expression was silenced using siRNAs. HRG treatment of cells transfected with a luciferase reporter plasmid under the control of the murine bcl-X promoter which contains two progesterone response elements (PREs), resulted in an increase in luciferase activity. HRG had no effect on PR transcriptional activation when cells were transfected with a mutant vector containing a deletion spanning both PREs in bcl-X promoter. We assessed the specific association of Stat3 and PR to the PRE region of bcl-X promoter in the context of living cells by performing Chromatin Immunoprecipitation (chIP) Assays. We found that HRG treatment of primary cultures of C4HD cells induced PR and Stat3 recruitment to the bcl-X promoter. HRG also induced PR and Stat3 occupancy of the stably integrated MMTV promoter in T47D-Cat0 breast cancer cells. By performing sequential chIP assays we showed that HRG induced simultaneous PR and Stat3 occupancy of the bcl-X promoter region. We explored Stat3 role in the non-classical mechanism of action of PR, where PR is recruited to p21 promoter indirectly through interaction with Sp1 transcription factor. Interestingly, when cells were treated with HRG, we detected Stat3 binding to the Sp1 binding sites of the PR-regulated p21 promoter, together with Sp1 and PR. These results provide the first evidence that Stat3 modulates ligand-independent activation of PR by HRG in breast cancer cells.
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 2285. doi:10.1158/1538-7445.AM2011-2285
Abstract 2302: Detection of HMTV env sequences in hormonally dependent tissues
Authors: Pogo Beatriz GT , Moran Heberth , Marin Tania , Lee Anna , Deligdisch Liane , Ancaro Kathleen , Anderton Douglas , Melana Stella , Holland James F. 
Published: June 2012

Abstract
Breast cancers discovered during pregnancy or lactation (gestational) are known to be very aggressive and of poor prognosis. We have found a Mouse Mammary Tumor Virus (MMTV) like virus in human breast cancer, but not in adjacent normal tissue, indicating it exogenous origin. This virus, Human Mammary Tumor Virus (HMTV) recognized by its unique env sequence is present in 62% of gestational breast cancer, compared with 38% of sporadic breast cancers (Wang et al, 2003. Medical Oncology 20:233-236). The aggressive phenotype of gestational breast cancer was suggested to be due to the effect of hormones that stimulate cellular growth. HMTV- LTR contained sequences which are responsive to several hormones (glucocorticoid, estrogen, prolactin, and progesterone) and a transcription factor (TEF-1 family) (Wang et al, 2003. Medical Oncology 20:233-236).
To find if HMTV is present in other tissues that respond to hormones, we have investigated the presence of HMTV sequences in two of these tissues. Endometrium is a classical example of such tissue. Endometrial cancers and normal endometrium were analyzed for HMTV env sequences. The results indicated that HMTV env sequences were present in 3.4% of the normal tissues and 37% of the tumors analyzed. Recently, it was reported that MMTV-like sequence was found in 10% of endometrial cancers (Johal et al. 2010, J. Med. Virology; 82: 1044-50).
During lactation, the mammary gland experiences major metabolic changes due to hormonal stimulation. We have examined 88 normal milks and 63 milks from women, who have undergone biopsies. Whereas in the cells of normal milks 8% showed env sequences cells in the milk of the biopsied group showed that 23.8% contain HMTV sequences.
These results confirmed electron microscope observations that a betaretrovirus was present in milk from healthy women and those with breast cancer (Moore et al. 1971, Nature 229: 611-615).
Taken together, the results presented here suggest that tissues and tumors stimulated by hormones showed high prevalence of HMTV sequences.
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 2302. doi:10.1158/1538-7445.AM2011-2302