bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5769: Comprehensive analysis of genomic alteration in histologic components of myxoid liposarcoma
Authors: Chae Jee Hoon , Kim Sun il , Kim Do Hee , Kim Sangkyum , Choi Junjeong 
Published: June 2022

Abstract
Purpose: Myxoid liposarcoma (MLS) is the most common type of liposarcoma in humans. Tumor with round cell component shows poor clinical prognosis. Currently, specific target therapies for this tumor type have not been developed. We performed next-generation sequencing (NGS) analysis of paired samples to investigate genomic alteration in MLS with two histologic features.
Methods: Whole exome sequencing (WES) and transcriptome sequencing data were acquired from formalin-fixed paraffin-embedded samples of 10 patients. We performed differential gene expression analysis and pathway analysis between the conventional myxoid liposarcoma area lesion and that of round cell component using transcriptome sequencing data. In addition, we analyzed characteristics of mutational signatures in the two histologic features of MLS using WES data.
Results: CD37 showed the most significant expression in round cell components of myxoid liposarcoma (RMLS) compared to conventional MLS. The immune response pathway was significantly enriched in the conventional lesion. The pathway involving cell mitotic and metabolic processes were represented considerably in with RMLS. FUS-DDIT3/EWSR1-DDIT3 fusion oncogene was detected in these RMLS samples more frequently than MLS. Some patients showed mutational signatures related to oxidative stress.
Conclusion: The expression of CD37 was highly expressed in almost all the RMLS. We identified smoking profile signature characteristics in these two samples, but no significant mutational difference was placed between the RMLS and MLS samples. In RMLS, the fusion oncogene and other overexpression oncogenes that occur in the cell cycle affect lipid metabolism due to oxidative stress such as ROS. Finally, we observed CD37 expression by performing IHC only in RMLS samples. The above data suggest that CD37 and other markers can be a promising biomarker target in myxoid liposarcoma with unfavorable histological features.
Citation Format: Jee Hoon Chae, Sun il Kim, Do Hee Kim, Sangkyum Kim, Junjeong Choi. Comprehensive analysis of genomic alteration in histologic components of myxoid liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5769.
Abstract 5771: The refined stratification of receptor tyrosine kinase fusions in lung cancer
Authors: Liang Chaoyang , Li Lin , Liu Xiaofang , Liu Qiuhua , Wang Baoming , Wang Chunyang , Ma Tonghui , Meng Fanlu 
Published: June 2022

Abstract
Background: The overall survival of patients with the actionable receptor tyrosine kinase (TRK) fusions can be significantly prolonged after taking targeted kinase inhibitors. However, the outcomes are variable due to the different fusion types of the same driver gene.
Method: Formalin fixed paraffin embedded tissues from patients with lung cancer between March 2018 and September 2021 were performed by using next generation sequencing (NGS) at Genetronhealth, a laboratory accredited by College of American Pathologists and Clinical Laboratory Improvement Amendments.
Results: In a large cohort of 3768 patients with lung cancer, 348 cases harboring the actionable TKR fusions, including ALK, ROS1, RET, EGFR, MET, BRAF, NTRK1/2/3. TRK fusions can be divided into three types based on the breakpoints, partners and fusion models: single 3’ fusions, nonreciprocal fusions with the intact tyrosine kinase domain (TKD); single 5’ fusions, reciprocal fusions with the incomplete TKD; complex fusions, nonreciprocal/reciprocal fusions or nonreciprocal fusions with different partners. At the gene level, 58% (203 of 348) of TRK fusions were ALK, among which 71% of single 3’ ALK (144 of 203), 3% of single 5’ ALK (6 of 203) and 26% of complex fusions (53 of 203) were included. ROS1 fusions accounted for 14% (50 of 348) of all TRK fusions, and the proportions of single 3’ fusions, single 5’ fusions and complex fusions were 60% (30 of 50), 6% (3 of 50) and 34% (17 of 50), respectively. RET captured 19% (66 of 348) TRK fusions with 70% of single 3’ RET (46 of 66), 5% of single 5’ RET (3 of 66) and 26% of the complex fusions (17 of 66). EGFR owned 3% (9 of 348) with 33% of single 3’ EGFR (3 of 9), 33% of single 5’ EGFR (3 of 9) and 33% of the complex (3 of 9). MET, BRAF and NTRK1/2/3 shared the rest 5% of total fusions without complex type.
Conclusion: Our research shows different types of TRK fusions in Chinese lung cancer patients, which can help guide the precise treatment in clinical.
Citation Format: Chaoyang Liang, Lin Li, Xiaofang Liu, Qiuhua Liu, Baoming Wang, Chunyang Wang, Tonghui Ma, Fanlu Meng. The refined stratification of receptor tyrosine kinase fusions in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5771.
Abstract 5772: Differences in clinical actionability by comparing mutational landscape of young and old breast cancer patients
Authors: Liu Jiaqi , Jia Ziqi , Liu Gang , Wang Xiang , Meng Qi , Wang Sha , Shao Yang 
Published: June 2022

Abstract
Background: Early-onset breast cancer (BC) is associated with poor prognosis, which is also characterized by high recurrence risk, distant metastases and advanced stages at the time of diagnosis. While germline mutations in BRCA1/2 are known to underlie a subset of early-onset BC cases, the clinical and genetic characteristics in other young BC patients remain to be explored.
Method: We profiled primary lesions from 440 Chinese female BC patients by using a 425-cancer-gene panel. The population was sub-divided into young (≤40 years old) and old (&gt;40 years old) BC patients according to ages at diagnosis. Young and old BC patients were compared for their associations with genomic aberrations, with focus on existing BC targetable alterations, including those in the ERBB2 gene and PI3K and homologous recombination repair (HRR) pathways.
Results: 137 (31.1%) patients presented with BC at a young age (median age=35 [18-40]) and 303 (68.9%) with BC diagnosed at an older age (median age=53 [41-82]) in our study cohort. TP53 (young, 61.3%; old, 67%), PIK3CA (33.6% and 41.3%), and GATA3 (9.5% and 8.3%) were among the top frequently altered genes in both subgroups. A total of 70 patients carried pathogenic germline mutations. Of these, 57.3% were alterations in the HRR pathway genes, including BRCA1/2, WRN, BLM, and PALB2, etc, with comparable frequencies in young and old patients. Germline BRCA1/2 mutations were detected in nine (6.6%) and 23 (7.6%) of the young and old patients, respectively. Somatic BRCA1/2 mutational frequencies were also comparable between young (8.8%) and old (9.9%) patients. Overall, somatic alterations in HRR pathway genes were detected in 32.1% young and 40.6% old BC patients. While similar frequencies of ERBB2 amplification (14.6% vs. 18.2%; P= 0.41) were detected in young and old BC patients, older patients carried more ERBB2 mutations (1.5% vs. 7.3%, P= 0.01). Interestingly, the highest rate of ERBB2 amplification was observed in the 20-30 years age group. Alterations in NF1 (10.6% vs. 3.6%, P=0.02) and PKHD1 (6.9% vs. 2.2%, P=0.04) were more frequent in older patients. Alterations in the PI3K pathway genes were more enriched in the older BC patients with overall mutational frequencies of 55.5% and 68.6% (P=0.01) in young and old subgroups, respectively. Finally, we observed an age-dependent increase in tumor mutational burden.
Conclusion: BC in young and old patients exhibited different genomic characteristics that could be taken into consideration for treatment recommendations.
Citation Format: Jiaqi Liu, Ziqi Jia, Gang Liu, Xiang Wang, Qi Meng, Sha Wang, Yang Shao. Differences in clinical actionability by comparing mutational landscape of young and old breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5772.
Abstract 5789: Multi-omic artificial intelligence outcome modeling of ovarian cancer, phase I: Whole exome and whole transcriptome data
Authors: Orr Brian , Edwards Robert P. , Radolec Mackenzy 
Published: June 2022

Abstract
Background: Over a decade ago, the Cancer Genome Atlas (TCGA) provided the initial genomic characterization of ovarian cancer with targeted exome capture and sequencing. Unlike other TCGA analysis, they were unable to identify prognostic mutational profiles outside of BRCA status. There has been limited characterization of the ovarian cancer genomic profile since. Our objective presented here was to perform whole exome and whole transcriptome analysis of 241 ovarian cancer samples and compare to the TCGA dataset. This is the first phase of a muti-step ongoing analysis wherein we will input and correlate the complete genomic profile, complete patient outcome data, and immunohistochemical staining into a multi-omic artificial intelligence (AI) machine learning model with the aim of improved individualized outcome prediction.
Methods: Tumor samples from 2000-2016 were obtained at time of surgery under approved University of Pittsburgh approved IRB consent. Whole exome and whole transcriptome sequencing were performed in collaboration with Helomics Corporation. Sequencing analysis was compared to TCGA data.
Results: 241 patient samples underwent sequencing analysis. Similar to TCGA, most mutations were missense. I am having a difficulty interpreting the magee vs tcga comparison graphs, how to discuss the TP53 and BRCA comparison without using the lollipop charts and highlighting the rna-seq data into written form. Please add.
Conclusions: We present our findings of one of the largest molecular characterizations of ovarian cancer. Similar to the TCGA, there is noted heterogeneity to the genomic profile of ovarian cancer. Multi-omic AI outcome modeling has the potential to overcome the gap defining prognostic sub-groups so that we can tailor therapies to the individual
Citation Format: Brian Orr, Robert P. Edwards, Mackenzy Radolec. Multi-omic artificial intelligence outcome modeling of ovarian cancer, phase I: Whole exome and whole transcriptome data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5789.
Abstract 5799: Landscape of TSC1 and TSC2 mutations in patients with advanced solid cancers
Authors: Gulati Gunsagar S. , Cacheris William , Dutta Ritika , Ahnert Jordi Rodon 
Published: June 2022

Abstract
Tuberous sclerosis proteins 1 and 2 (TSC1 and TSC2) are tumor suppressor genes and inhibitors of the mammalian target of rapamycin (mTOR) pathway. Mutations in these genes are candidates for novel mTOR inhibitors, such as nanoparticle albumin-bound (nab)-sirolimus, which have already demonstrated clinical efficacy in isolated case studies of patients with mutations in the mTOR pathway. However, the incidence of TSC1 and TSC2 mutations in the US and its distribution across tumors has not yet been systematically reported. Moreover, existing models for calculating incidence of targetable mutations do not account for cross-eligibility for other clinically approved targets. Therefore, here, we describe the landscape of TSC1 and TSC2 mutations across 16 solid tumors from The Cancer Genome Atlas (TCGA; n = 9,808 patients) and AACR GENIE database (MSK: n = 14,340 patients, DFCI: n = 5,271 patients) and estimate the annual incidence of eligible patients using the Surveillance, Epidemiology, and End Results Program (SEER) database. We then refined these estimates by excluding patients eligible for immunotherapy (tumor mutational burden (TMB) &gt; 10 mutations/Mb) and other targeted therapies (n = 23 FDA-approved drug-targetable mutations). We find that the combined US incidence of patients with truncations (e.g. frameshift, nonsense, splice-site) or deep copy number deletions in TSC1 and TSC2 is ~11,000 ± 1,000 (mean Spearman ρ across datasets: 0.92). About 40% of these patients have mutations in at least one of 23 other drug-targetable genes. TSC1 and TSC2 mutations were most frequent in bladder and hepatobiliary cancers, respectively, with the absolute prevalence of mutations being highest in bladder and non-small-cell lung cancer. Among the patients with TSC1 and TSC2 mutations with other targetable mutations, we identified the most common co-occurring targetable mutations with TSC1 and TSC2, suggesting that combination or sequential treatment with immunotherapy and BRAF and FGFR3 inhibitors are possible options for clinical trials. Finally, we show that the combined annual US incidence of patients with TSC1 and TSC2 mutations is on average (n = 3 clinical genomic cohorts) higher than 17 of 23 other common targetable mutations. Our approach is now being used to estimate the population size of other medically relevant mutations and identify associated genomic targets for improved clinical trial design.
Citation Format: Gunsagar S. Gulati, William Cacheris, Ritika Dutta, Jordi Rodon Ahnert. Landscape of TSC1 and TSC2 mutations in patients with advanced solid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5799.
Abstract 583: Improving anti-tumor response by increasing mitochondrial respiration of T-cell
Authors: Wu Meng-Han , Giddlings Emily , Danis Catherine , McCalab Megan , Kohler Mark Eric , Rincon Mercedes 
Published: June 2022

Abstract
Chimeric antigen receptor (CAR)-T cell therapy is revolutionary as a promising approach of cancer immunotherapy against lymphoblastic leukemia and lymphoma. While initially effective in up to 90% of patients with B-cell lymphoblastic leukemia, over 40% of patients will relapse, with sub-optimal persistence of functional CAR-T cells underlying many of these relapses. The major challenges of CAR-T cell to effectively eliminate cancer cells are extending persistence of CAR-T cells and retaining the effector function of CAR-T cells in vivo after prolonged in vitro expansion. To overcome such limitations, enhancing mitochondrial metabolism is emerging as an appealing approach to regulate CAR-T cell function, however, increasing mitochondrial respiration and ATP production is a challenging strategy. We have previously identified MCJ/DnaJC15 as an endogenous negative regulator of Complex I of electron transport chain. The absence of MCJ in CD8 cells (MCJ KO CD8 cells) increases Complex I activity, mitochondrial membrane potential, and mitochondrial respiration without affecting glycolysis. Lack of MCJ enhances cytokine secretion and cytotoxicity (two processes dependent on mitochondrial ATP) in CD8 cells in vitro and in vivo. Using the B16 melanoma cell model, we have shown that antigen-specific MCJ KO CD8 cells are superior in killing melanoma cells in vitro and in vivo. We have generated WT and MCJ KO CD19-41BB CAR-T cells and tested their anti-tumor activity against B-cell leukemia. The results reveal that MCJ-deficient CAR-T cells exhibit superior killing capacity against leukemia B cells and prolong survival of the leukemia-bearing mice. Together, these data demonstrate MCJ as an attractive target to enhance CAR-T cell therapy efficacy.
Citation Format: Meng-Han Wu, Emily Giddlings, Catherine Danis, Megan McCalab, Mark Eric Kohler, Mercedes Rincon. Improving anti-tumor response by increasing mitochondrial respiration of T-cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 583.
Abstract 5835: Functional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma
Authors: So Shan Shan , Yu Valen Z. , Law Simon Y. , Lung Maria L. 
Published: June 2022

Abstract
Esophageal squamous cell carcinoma (ESCC) is highly prevalent in Asia with a poor prognosis and a high mortality rate [1, 2]. The p63 protein, encoded by TP63, is a master regulator involved in many cell events including cell cycle, DNA damage, cell proliferation, stem cell maintenance, and cell death in different cancer types. ΔNp63α is the dominantly expressed isoform of p63 in squamous cell carcinomas, playing a critical role in tumorigenesis [3, 4]. However, the functional roles of ΔNp63α in ESCC have not been fully elucidated. Our results have revealed that ΔNp63α is highly expressed and up-regulated in ESCC. We have shown that ΔNp63α protein expression plays an oncogenic role in ESCC cells, depletion of which inhibits in vitro cell proliferation and colony formation and greatly suppresses in vivo tumor growth, in a panel of ESCC cell lines and our latest patient-derived organoid cultures, potentially in a differentiation-dependent manner. Glycolysis pathway and two novel downstream signaling pathways of ΔNp63α, MYC/4EBP1 and AKT/NDRG1, are significantly suppressed upon ΔNp63α depletion in ESCC cell lines. Notably, xenografts of ΔNp63α-depleted human ESCC cells show elevated infiltrating cancer-associated fibroblasts (CAFs), which may contribute to tumor suppression by ΔNp63α depletion. These data not only shed light on the ΔNp63α functions and how they contribute to the ESCC tumorigenesis, but also unravel potential therapeutic benefits for ESCC patients in the future. Acknowledgements: We acknowledge DSMZ (German Collection of Microorganisms and Cell Culture) for the KYSE cell lines. We acknowledge the Research Grants Council Theme-Based Research Scheme grant T12-701/17-R to MLL. References [1] Chen, W., et al., Cancer statistics in China, 2015. CA Cancer J Clin, 2016. 66(2): p. 115-32. [2] Peng, L., et al., CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population. Genomics Proteomics Bioinformatics, 2018. 16(4): p. 262-268. [3] Fukunishi, N., et al., Induction of DeltaNp63 by the newly identified keratinocyte-specific transforming growth factor beta Signaling Pathway with Smad2 and IkappaB Kinase alpha in squamous cell carcinoma. Neoplasia, 2010. 12(12): p. 969-79. [4] Moses, M.A., et al., Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis. Int J Mol Sci, 2019. 20(14).
Citation Format: Shan Shan So, Valen Z. Yu, Simon Y. Law, Maria L. Lung. Functional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5835.
Abstract 5873: Distinct prevalence and spectrum of germline cancer susceptibility gene mutations between early-onset and late-onset colorectal caner
Authors: Gao Zhidong , Zhou Jing , Xin Ying , Liang Bin , Shen Kai , Guo Peng , Jiang Kewei , Yin Mujun , Yang Xiaodong , Shen Zhanlong , Zhang Hui , Huang Depei , Ye Yingjiang 
Published: June 2022

Abstract
Background: In the past few decades, the incidence of early-onset CRC (&lt;50 years of age) has increased globally. Previous studies with small sample sizes have shown that early-onset CRC appears to have a distinct clinical, pathologic, and molecular features compared to late-onset CRC (≥ 50 years of age). However, few studies in a large population have focused on the differences in germline gene mutation spectrums of these two groups of patients.
Methods: Hybrid capture-based next-generation sequencing (NGS) were performed in 5080 colorectal patients in a CAP/CLIA-approved laboratory (3DMed). NGS testing for germline mutations and MSI was implemented.
Results: Of 5080 colorectal patients, early-onset CRC was observed in 1305 (25.7%) patients. The incidence of germline mutation was higher in early-onset CRCs than late-onset CRCs (8.97% vs. 4.15%,OR=2.27, P&lt;0.0001). Consistently, the frequency of MSI-H was higher in early-onset CRCs (13.0% vs. 5.7%, OR=2.48, P&lt;0.0001). The most frequently mutated gene was MLH1 (3.07%) in early-onset CRCs, followed by MSH2 (1.69%), APC (1.0%), MSH6 (0.84%), PMS2 (0.38%), RAD50 (0.31%), CHEK2 (0.31%), MUTYH (0.23%), BRCA1 (0.23%), and BRCA2 (0.23%). The frequency of MMR gene mutations among early- and late-onset patients was 5.98% and 1.27%, respectively (OR=4.95, P&lt;0.0001). MMR gene mutations accounted for 60% of germline mutations of early-onset patients, while this percentage was lower for late-onset CRC (30%). Higher frequencies of APC, RAD50 and CHEK2 gene mutations were associated with early-onset CRCs (all P&lt;0.05). The mutation frequencies of other DDR genes, MUTYH, BRCA1, BRCA2, ATM, ATR, FANCD2, TP53, were not statistically different between the two groups. The late-onset CRC tended to harbor a wider spectrum of germline cancer gene mutations, including an additional 14 cancer-related gene that were not found in early-onset CRC.
Conclusions: Our findings revealed different prevalence and spectrum of germline cancer gene mutations between early-onset and late-onset CRC, suggesting that young patients should be specially considered.
Citation Format: Zhidong Gao, Jing Zhou, Ying Xin, Bin Liang, Kai Shen, Peng Guo, Kewei Jiang, Mujun Yin, Xiaodong Yang, Zhanlong Shen, Hui Zhang, Depei Huang, Yingjiang Ye. Distinct prevalence and spectrum of germline cancer susceptibility gene mutations between early-onset and late-onset colorectal caner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5873.
Abstract 5878: The prognostic model of colorectal liver metastases contribute extended molecular profiling
Authors: Cui Chunhui , Wang Xintong 
Published: June 2022

Abstract
Background: Over half of colorectal cancer (CRC) patients will metastasize at the same/different times, Only 15-20% of patients are considered resectable at the time of diagnosis. The clinical situation attributed to the clinical heterogeneity of metastatic colorectal cancer(mCRC), the prognosis of patients with mCRC at different metastatic sites is different. The proportion of higher is colorectal liver metastasis (CRLM) and the mechanism of CRLM is complicated,studies have found cancer-related genes expand the predictive molecular profile of survival, The aim of this analysis was to verify and further develop the genetic risk scores.
Methods: In this study, bioinformatics methods were used to comprehensively analyze the CRLM cohort (n=270) in the database. The cohort patients were divided into high-risk group and low-risk group. Independent data (n=105) verified the prognostic validity of the model.
Results: The models established by commonly genes(APC, BRAF, ERBB2, KRAS, NRAS, PIK3CA, TP53, SMAD2-4) of CRLM were confirmed by prognostic markers. Differences between high-risk prognostic groups compared to low-risk were significant (HR = 1.9023, 95% CI: 1.61-2.23, P_value &lt;0.001), risk score can be used as biomarkers for constructing prognosis. we found significantly higher proportion of low-risk group diagnosed in stage I (82% vs 18%, P_value = 0.035), This model can distinguish in diagnosed stage I CRLM patients with poor prognosis, the model also has a good prognostic effect in validating data and clinical staging.
Conclusions: We found that the survival OS of the model risk-high cohort was significant, and is helpful for subsequent treatment.The model risk score was established to be superior to common biomarkers for CRLM, and the discovery of the model is helpful for find metastatic progression the treatment of patients with CRLM.
Citation Format: Chunhui Cui, Xintong Wang. The prognostic model of colorectal liver metastases contribute extended molecular profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5878.