bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1181: Structure and evolution of double minutes in a pediatric high-grade glioma
Authors: Xu Ke C. , Ding Liang , Chang Ti-Cheng , Wang Shuoguo , Wang Yong-Dong , Mulder Heather , Shao Ying , Easton John , Zhang Jinghui , Baker Suzanne J. , Wu Gang 
Published: August 2018

Abstract
Double minutes (DMs) are circular extrachromosomal DNA frequently found in brain tumors, often associated with overexpression of oncogenes. To understand the evolution of DMs, we developed a graph-based method to identify simple cycles in a directed graph consisting of highly amplified copy number alteration (CNA) segments and structural variants (SVs) found at the boundaries of each segment. With this method, we presented a case of DM evolution in a pair of diagnosis and relapse whole genome sequencing (WGS) samples from a pediatric high-grade glioma patient, followed by validation with Chromium linked-read sequencing. Using an empirical value of CNA threshold, we extracted 44 and 29 highly amplified CNA segments from the diagnosis and relapse samples respectively. We then identified 29 and 19 unique SVs associated with these CNA segments from the two samples. We constructed five major DMs in the diagnosis sample and five major DMs in the relapse sample, covering all the CNA segments and the SVs. One DM harboring EGFR is identified in both samples. Two of the five relapse DMs are also found in the diagnosis sample but in a trace amount, suggesting a shifting from minor clones in the diagnosis to dominant clones in the relapse. Two major DMs, one carrying MYC and the other carrying CDK6, were only identified in the relapse sample. Analysis of mutations on the DMs revealed that new somatic mutations were acquired on sub-populations of the DMs. Importantly, for the EGFR-carrying DM shared in both samples, we identified an 8-bp deletion at a splicing site of EGFR that has 2% allele frequency in the diagnosis but reached 96% in the relapse. This deletion leads to a mRNA transcription skipping of exon 16 with an 87 fold up-regulation of EGFR compared with other high-grade gliomas, suggesting a possible drug resistance mechanism and positive selection of tumor cells resulting from the mutated DM. We propose an evolutionary model that simultaneously involves a branching model for DM formation and a selection model for mutations on DM. We applied the same methods to the WGS data from two adult glioblastoma patients in TCGA, and found that our proposed model could also explain the DM evolution in these patients. Therefore, our study reveals that DMs follow an evolutionary trajectory independent of linear chromosomes and contribute to tumor heterogeneity.
Citation Format: Ke C. Xu, Liang Ding, Ti-Cheng Chang, Shuoguo Wang, Yong-Dong Wang, Heather Mulder, Ying Shao, John Easton, Jinghui Zhang, Suzanne J. Baker, Gang Wu. Structure and evolution of double minutes in a pediatric high-grade glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1181.
Abstract 1195: Incidence rates of head and neck cancer across Thailand and the USA
Authors: Argirion Ilona , Rentschler Katie , Vatanasapt Patravoot , Sriplung Hutcha , Rozek Laura S. 
Published: August 2018

Abstract
Background: Head and neck cancer is the sixth most common cancer in the world, with the largest burden occurring in developing countries. Although the primary risk factors have been well characterized, little is known about the temporal trends in head and neck cancer across Thailand. Using population based registries from three Thai provinces (Songkhla, Lampang and Khon Kaen), we have characterized the age-standardized incidence rates of head and neck cancer by sex and age and compared them to those observed in the United States. Methods: Cancer cases diagnosed between 1990 and 2014 were selected by ICD-10 code directly from the Songkhla, Lampang and Khon Kaen Cancer Registries as well as the Surveillance, Epidemiology, and End Results Program (SEER) for the following sites: oral cavity (00, 03-06), tongue (01-02), pharynx (09-10, 12-14), and larynx (32). The data were analyzed using R software (3.1.1) and Joinpoint Regression Software (4.4.0) to determine age-standardized incidence rates and trends of annual percent change. Incidence rates were standardized using the Segi (1960). Additional exploratory analyses using stratified linear regression models were conducted to assess temporal trends in head and neck cancer across 10-year age groupings. Results: Overall head and neck cancer rates are decreasing across all registries except Khon Kaen, where there is an observed, albeit not statistically significant, increase among males (APC: 0.53, p=0.3). Subsite analyses demonstrate consistent decreases in both larynx and oral cavity cancers, but suggested increases in pharynx and tongue cancers among both genders in the US (APC: 1.9 and 1.6, p&lt;0.05 respectively) as well as pharynx cancer in Khon Kaen males (APC: 2.1, p&lt;0.05). Furthermore, age-stratified APC analyses showed increased incidence in tongue cancer among Khon Kaen females age 30-39, Khon Kaen males age 30-59, Lampang males age 50-59, Songkhla females age 30-49, US females age 30-49 and 70-85+, as well as US males age 40-79. Pharynx cancers were seen to increase in Khon Kaen males age 40-59 and US males age 50-59. Conclusions: Although overall trends in head and neck cancer do seem to be decreasing across both Thailand and the United States, there is reason to believe that the etiological shift affecting both pharynx and tongue cancers in the US may be similarly presenting in Thailand. While disparities across gender and region do still exist, further investigation into the increased rates of early onset cancer is needed.
Citation Format: Ilona Argirion, Katie Rentschler, Patravoot Vatanasapt, Hutcha Sriplung, Laura S. Rozek. Incidence rates of head and neck cancer across Thailand and the USA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1195.
Abstract 1198: Rare isn't rare: Rare cancers compose over 50% of all U.S. diagnoses
Authors: Arline Katherine , Zeme Emily , Treuting Robert L. , Bravo Rodrigo , Barber Jamie , Higginson Christopher , Goetz Jon , Siders William , Kaplan Johanne 
Published: August 2018

Abstract
Rare cancers are an understudied and deadly public health problem. Estimates for the percentage of cancer diagnoses that are rare vary depending upon the source cited and the definition of what constitutes a rare cancer. A frequently cited report states that 25% of all adult cancers are rare. However, given the ever-changing landscape of cancer biology and as a result of changes in disease classification, oft-cited percentages underestimate the burden of rare cancers. To address this discrepancy, we reviewed the most recent publicly available data regarding the incidence of all cancers in the United States. Following the NCI definition of a rare disease as one affecting fewer than 15 persons per 100,000 per year, for 2017, a cancer affecting 48,952 or fewer is classified as rare. We considered each cancer individually, acknowledging subtypes based upon the criteria of scientifically accepted definitions, treatments, and histology. We then compiled statistics for each type and subtype. By this method, the total number of estimated new cancer patients in 2017 was 1,685,346, which differed only 0.2% from the Cancer.gov's publicly available estimate of 1,688,780. However, in contrast to previously published data that indicated that 60 of 71 cancer types were rare, we identified a total of 347 cancers, of which 337 were rare. The estimate for rare cancer diagnoses in the U.S. per year was therefore 875,084. Ultimately, 51.9% of all cancer diagnoses are classified as rare cancers by this method. In addition, of 52 major groupings of cancer, 35 (67.3%) disproportionately affect minorities in terms of incidence or overall survival. Seven groupings exclusively or almost exclusively affect women, and 7 additional groups display disproportionate incidence or negative outcomes in women. In addition, while many cancers affect children, and while all cancer in children is rare, at least 55 cancers exclusively or frequently affect children. This analysis clearly shows that the incidence of rare cancer in the United States is widely misunderstood and that cancer in total disproportionately affects historically underserved populations. Treatment options are needed for each form of cancer and should be developed based on a thorough understanding of each disease's biology. In addition, efforts to understand and address the origins of demographic disparities can help reduce disease burden.
Citation Format: Katherine Arline, Emily Zeme, Robert L. Treuting, Rodrigo Bravo, Jamie Barber, Christopher Higginson, Jon Goetz, William Siders, Johanne Kaplan. Rare isn't rare: Rare cancers compose over 50% of all U.S. diagnoses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1198.
Abstract 1199: Adult Hispanic males experience a higher incidence of acute lymphoblastic leukemia compared to non-Hispanic Whites
Authors: Espinoza-Gutarra Manuel R. , Munoz Edgar , Shah Dimpy P. , Karnad Anand , Mesa Ruben A. , Ramirez Amelie G. 
Published: August 2018

Abstract
Introduction: Acute leukemia is an important cause of morbidity and mortality with differences in incidence and outcomes between patients of different ethnic backgrounds. We conducted this study to examine the ethnic disparities in incidence of ALL as well as other types of acute leukemia in the Latino population in South Texas.
Methods: Data were obtained from the U.S. Surveillance, Epidemiology and End Results 18 (SEER) Program and the Texas Cancer Registry (TCR) under Limited-Use Data Agreements between sources and authors. Adult patients (15 years or older) were identified in both SEER and TCR databases from 2000 to 2014 and ICD-O-3 codes were used to select specific malignancies: ALL (9727-9729, 9835-9837), acute promyelocytic leukemia (APL) (9866) and non-APL acute myeloid leukemia (AML) (9840, 9861, 9867, 9870-9874, 9891, 9895-9897, 9910, 9920, 9930, 9931). Ethnicity was classified as Hispanic (H) and non-Hispanic White (NHW) per the North American Association of Central Cancer Registry (NAACR) Hispanic Identification Algorithm. Cases were obtained from SEER 18 and TCR, including Texas and the 38 counties of South Texas. Comparisons used the SEER population of NHW as reference. We used SEER*Stat software v 8.3.4 (SEER*Stat, NIH), to generate 2000-2014 average annual age-specific and age-adjusted acute leukemia incidence rates (per 1000000), rate ratios (RR) and 95% confidence interval (CI) for Hispanic and NHW populations in SEER, Texas, and South Texas.
Results: Table 1 shows Hispanic males in South Texas had significantly higher RR for development of ALL (p&lt;0.05), and lower for non-APL AML; there was no statistical difference for APL RR compared to NHW. Males (15-39 and 70-79 years) had higher rates of ALL.
Conclusion: Latinos in South Texas experience a higher incidence of ALL and a lower incidence of non-APL AML compared to NHW. Future studies are needed to identify specific risk factors associated with this higher burden in Hispanic population.
Table 1SEERTCRTexasSouth TexasHNHWRR (95%CI)HNHWRR (95%CI)HNHWRR (95%CI)ALL213744421.50 (1.42-1.59)9789851.43 (1.33-1.53)3771071.63 (1.46-1.81)Non-APL AML3398047190.77 (0.75-0.80)216375930.41 (0.40-0.43)8488980.48 (0.45-0.51)APL77022241.22 (1.11-1.33)3094720.90 (0.80- 1.02)109510.94 (0.77- 1.14)
Citation Format: Manuel R. Espinoza-Gutarra, Edgar Munoz, Dimpy P. Shah, Anand Karnad, Ruben A. Mesa, Amelie G. Ramirez. Adult Hispanic males experience a higher incidence of acute lymphoblastic leukemia compared to non-Hispanic Whites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1199.
Abstract 1207: A systematic literature review of the prevalence of PIK3CA mutations and mutation hotspots in HR+/HER2- metastatic breast cancer
Authors: Mollon Lea , Aguilar Alejandra , Anderson Elizabeth , Dean Joni , Davis Lisa , Warholak Terri , Aizer Ayal A. , Platt Emma , Bardiya Aditya , Tang Derek 
Published: August 2018

Abstract
Introduction: Clinical research on the predictive value of PIK3CA mutations in hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2–) metastatic breast cancer (mBC) has advanced in recent years. However, knowledge of epidemiological prevalence has not been systematically evaluated. This study aimed to report prevalence of PIK3CA mutation using different biopsy techniques as well as specific hotspot mutations across the available literature.
Methods: A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts was performed by two independent researchers that included, but was not limited to, keywords: “breast neoplasm”, “PIK3CA protein”, “hormone receptor positive”, and “metastases”. English-language studies in HR+, HER2– mBC detailing the prevalence of PIK3CA mutations and published between January 1993 through August 2017 were included. Content analysis was employed to quantify collected data elements.
Results: Of 558 studies included for full-text review, 36 met inclusion criteria. Most included studies (n = 18) were observational in nature. A total of 4,247 samples were tested for genetic mutations. Most studies used tissue biopsy samples (n = 33; 89%). Tumor samples accounted for 84.6% of all samples (n = 3597). Liquid biopsies were performed in 4 studies (11%) and accounted for 15.3% of all samples (n = 650). One study reported both liquid and tumor biopsy data. Overall, reported prevalence of the PIK3CA mutation ranged from 13.3% to 61.5%. Median prevalence was 36.4% (25th percentile = 28.6%; 75th percentile = 48.4%). Among studies using tissue biopsies, the majority reported prevalence from 16.7% to 61.5%. Among studies using liquid biopsies, the majority (n = 3) reported prevalence from 43.3% to 46.8%; one other study reported 13.3%. The most commonly tested hotspot mutations were H1047R and E545K. Among studies reporting specific hotspot mutation prevalence (n = 9), the H1047R hotspot mutation prevalence in these studies ranged between 25% and 75% while the E545K prevalence ranged between 11.1% and 50%.
Conclusions: Although discrepancies exist with respect to mutation prevalence estimated across various tissue vs. liquid biopsy techniques, PIK3CA mutations and mutation hotspots (specifically H1047R and E545K) frequently occur in HR+/HER2– mBC.
Citation Format: Lea Mollon, Alejandra Aguilar, Elizabeth Anderson, Joni Dean, Lisa Davis, Terri Warholak, Ayal A. Aizer, Emma Platt, Aditya Bardiya, Derek Tang. A systematic literature review of the prevalence of PIK3CA mutations and mutation hotspots in HR+/HER2- metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1207.
Abstract 1214: Nasopharyngeal carcinoma clinical stage, histologic grade and biomarker status at presentation are usually of poor prognostic characteristics: A clinicopathologic study in a low-resource setting
Authors: Olusanya Aralola A. , Ogun Gabriel O. , Adeyemo Adebolajo 
Published: August 2018

Abstract
Introduction: Nasopharyngeal carcinoma (NPC) is the 8th commonest malignancy in men and the commonest head and neck tumor in Ibadan Cancer Registry (IBCR).
Methods: Clinical files and records of all nasopharyngeal carcinoma diagnosed at the Department of Pathology, University College Hospital affiliated with IBCR between January 2007 and December 2016 were reviewed for demographic data, clinical presentation, clinical stage, histologic grade, LMP-1 and EGFR status.
Results: A total of 71 cases of nasopharyngeal carcinoma were diagnosed during the study period, comprising 44 males and 27 females with a male:female ratio of 1.6. Age ranged from 12 years to 80 years, the modal age group was 40-49 and the modal age was 45 years. Sixty-three percent of cases were non-keratinizing undifferentiated tumors, 31% were non-keratinizing differentiated, 4.2% were keratinizing tumors and 1.4% basaloid squamous cell carcinoma. In all, non-keratinizing undifferentiated tumors constituted 64% of tumors in males and 63% in females. Conversely, non-keratinizing differentiated tumor was commoner in males, accounting for 34% of tumors compared to only 26% in females. Also, keratinizing tumor was twice as common in females than males; there was only a single basaloid squamous cell carcinoma recorded. The age group 30-39 years had the highest incidence of non-keratinizing undifferentiated tumor while non-keratinizing differentiated tumor was more common in the 40-49 age group. Patients presented most frequently with stage II disease, which accounted for 62% of cases. About 20% of these patients presented with stage IV disease. Nasal and aural symptoms accounted for the commonest presenting complaint, occurring in 38% of patients. Thirty-six percent presented with nasal symptoms alone while 13% had a combination of nasal, aural and visual symptoms; this group was mainly patients with stage IV disease. LMP-1 positivity was observed in as many as 99% of all cases. EGFR was positive in 94% of cases, indicating that NPCs are usually of poor prognosis in our practice setting at presentation.
Conclusion: In our practice, nasopharyngeal carcinoma is characterized by late-stage presentation, high-grade histologic characteristics and have biomarker indicators of poor prognosis.
Citation Format: Aralola A. Olusanya, Gabriel O. Ogun, Adebolajo Adeyemo. Nasopharyngeal carcinoma clinical stage, histologic grade and biomarker status at presentation are usually of poor prognostic characteristics: A clinicopathologic study in a low-resource setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1214.
Abstract 1246: A family history of CRC confers protection against other cancers in a cohort of patients at risk for CRC
Authors: Tobi Martin , Antaki Fadi , Rambus MaryAnn , Lawson Michael , Ezekwudo Daniel 
Published: August 2018

Abstract
Risk for colorectal cancer (CRC) confers susceptibility to other cancers such as small bowel, breast, prostate, and female genital. However, these cancer family histories (F/H) have not been studied systematically.
Methods: 1,948 patients at increased CRC risk were followed to determine if the biomarker outcome was related to personal cancer prevalence or a cancer F/H by risk questionnaire which categorized patients as: Group 0 (no family history of cancer), Group 1 (F/H of breast cancer), Group 2 (F/H CRC), and Group 3 (P/H uterine/ovarian cancers).
Results: Demographics (age, sex, race, obesity) and NSAID use were similar in all groups and 88% were males. The proportion of cancer incidence in Group 1 is statistically greater [RR 1.36 (1.08-1.72) p = 0.014] compared to group 0 (Figure). Conversely, group 2 had statistically less cancer [RR 0.72 [0.52-0.99], p=0.045]. There was no significance difference between Group 0 and Group 3. About half the tumors in this older group of Veterans were prostatic. There was a wide variety of other cancers. In the entire cohort of the 5 tumors the most common tumor was prostate (n=222) followed by lung (n=61); CRC (n=53); bladder (n=23) and breast (n=20).
Conclusions: These differences may be explained by the effect of exosomes which play a major role in CRC and other cancers. Exosomes are nano-lipid particles of 30-100 nm released into the extracellular compartment. The ability of exosomes to facilitate cell-cell communication could be used to inhibit tumorigenic pathways. Exosomes may be endogenous in the case of CRC cell release or exogenous, found in breast milk containing microRNA moieties relevant to inhibition of carcinogenesis of cancers. Many of these mutated genes may inhibit tumorigenic process of cancers thus conferring protection against incipient cancers thus explaining our observation in Group 2. A commonality between CRC and endometrial cancer genetics potentially explains the reduced cancer prevalence in Groups 2 & 3. Breast cancer does not share BRCA “founder genes” with CRC and in contrast to CRC, K-ras mutations are not major events and thus F/H does not confer protection. This hypothesis remains to be proven but in the interim, timely screening for common cancers in patients with a family history of breast cancer may be effective.
Citation Format: Martin Tobi, Fadi Antaki, MaryAnn Rambus, Michael Lawson, Daniel Ezekwudo. A family history of CRC confers protection against other cancers in a cohort of patients at risk for CRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1246.
Abstract 1262: Type-2 cGMP-dependent protein kinase has a tumor-suppressive role in the colon epithelium
Authors: Islam Bianca N. , Sharman Sarah K. , Hou Yali , Ashby Justin , Wang Rui , Sridhar Subbaramiah , Kolhe Ravindra , Browning Darren D. 
Published: August 2018

Abstract
The cGMP level plays a central role in regulating homeostasis in the colon epithelium and is emerging as a potential target for colon cancer prevention. The signaling components downstream of cGMP, and the tumor suppressive mechanism remain poorly understood. The present study has examined the expression of cGMP-dependent protein kinase isoforms (PKG1, PKG2) in normal intestinal mucosa and in colon cancer from human specimens. Immunohistochemical analysis detected PKG1 in supportive cells in the lamina propria and in smooth-muscle tissue, but not in the epithelium of normal intestine and colon. In contrast, PKG2 was detected exclusively in the epithelium. In colon cancer, PKG1 was restricted to the stroma where it colocalized with vimentin, whereas PKG2 was only detected in the tumor epithelium where it colocalized with cytokeratin. This pattern of PKG isoform expression was similar in the mouse intestine and colon, where only PKG2 was detected in purified colonic crypts. PKG2 knockout (KO) mice were used interrogate possible anti-carcinogenic roles in the colon epithelium. When subjected to the AOM/DSS model of colon carcinogenesis, the PKG2 KO animals produced significantly more polyps than wild type controls (1.75-fold, p=0.0037). While the polyps from PKG2 KO animals were slightly smaller than those from wild type, the trend was not significant (p=0.13). Wild type and PKG2 KO mice responded equally to DSS treatment, but the PKG2-deficient animals exhibited crypt hyperplasia and increased apoptosis in luminal epithelium relative to wild type animals. Taken together these findings suggest that PKG2 has a tumor suppressive role in the colon epithelium, and that reducing the proliferative compartment may be part of the mechanism.
Citation Format: Bianca N. Islam, Sarah K. Sharman, Yali Hou, Justin Ashby, Rui Wang, Subbaramiah Sridhar, Ravindra Kolhe, Darren D. Browning. Type-2 cGMP-dependent protein kinase has a tumor-suppressive role in the colon epithelium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1262.