The prevalence of CDK12 alterations in Chinese cancer patients and the association with tumor mutation burden(TMB) and survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13663-e13663
Author(s):  
Ke Li ◽  
Xi Guo ◽  
Yunhua Mao ◽  
Mengmei Yang ◽  
Mengli Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Prostate Adenocarcinoma ◽  
Chinese Patients ◽  
Cyclin Dependent Kinase ◽  
Poor Prognostic Factor ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Pan Cancer

e13663 Background: Cyclin-dependent kinase 12 (CDK12) is a cyclin-dependent kinase that regulates transcription and RNA splicing, thereby modulating multiple cellular processes. It has been suggested that CDK12 loss-of-function mutations lead to a higher neoantigen burden and favorable responses to PD-1 inhibitors in advanced prostate cancer. Given this potentially actionable molecular subtype, we sought to determine the prevalence of CDK12 alterations in Chinese cancer patients and the association with TMB and overall survival(OS). Methods: The prevalence of CDK12 alterations were queried in 3D Medicines database with 15,745 Chinese cancer patients involved. Whole-exome sequencing data of 464 patients with prostate adenocarcinoma(PRAD) from the Cancer Genome Altas (TCGA) were downloaded to explore the association between CDK12 gene alteration and OS. And the association with TMB were analyzed in a cohort of 731 patients with various cancer types published by Memorial Sloan Kettering (MSKCC) (Samstein et al., Nature Genetics, 2019). Results: Any CDK12 and known or likely deleterious CDK12 mutations were identified in 598(3.8%) and 98(0.62%) patients, respectively. Across all cancer types, prostate adenocarcinoma(PRAD) was found to have the highest frequency of deleterious mutations(8.75%, 23/263), followed by breast cancer (4.97%, 25/503). Mutations were also detected in multiple cancer types including bladder cancer, ovarian cancer, lung cancer, colorectal cancer and so on with a frequency of less than 1%. CDK12 mutations were associated with shorter OS (HR = 15.25; 95% CI, 2.88-80.73; p < 0.001) in TCGA PRAD and cholangiocarcinoma datasets, which was not seen in other cancer types. Patients harboring CDK12 mutation had a significant higher TMB(p < 0.001) in the pan-cancer study of publicly-available cohort from MSKCC. Conclusions: CDK12 alterations existed across tumor types in Chinese patients with relatively high frequencies detected in PRAD and breast cancer and represent extremely rare events in multiple cancers. CDK12 mutation was a poor prognostic factor in PRAD and cholangiocarcinoma. In a pan cancer analysis patients with CDK12 mutation tended to have a significant higher TMB and may benefit from PD-1/L1 blockade immunotherapy.

Exploration of the MSI landscape in Chinese pan-cancer patient by Next-Generation Sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14576-e14576
Author(s):  
Xinlu Liu ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Correlation Analysis ◽  
Cancer Patients ◽  
Cancer Type ◽  
Multiple Tumor ◽  
Treatment Plans ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Pan Cancer

e14576 Background: Clinically, MSI had been used as an important molecular marker for the prognosis of colorectal cancer and other solid tumors and the formulation of adjuvant treatment plans, and it had been used to assist in the screening of Lynch syndrome. However, there were currently few reports on the incidence of MSI-H in Chinese pan-cancer patients. This study described the occurrence of MSI in a large multi-center pan-cancer cohort in China, and explored the correlation between MSI and patients' TMB, age, PD-L1 expression and other indicators. Methods: The study included 8361 patients with 8 cancer types from multiple tumor centers. Use immunohistochemistry to detect the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) in patients with various cancer types to determine the MSI status and detect the expression of PD-L1 in patients. Through NGS technology, 831 genes of 8361 Chinese cancer patients were sequenced and the tumor mutation load of the patients was calculated. The MSI mutations of patients in 8 cancer types were analyzed and the correlation between MSI mutations of patients and the patient's age, TMB and PD-L1 expression was analyzed. Results: The test results showed that MSI patients accounted for 1.66% of pan-cancers. Among them, MSI-H patients accounted for the highest proportion in intestinal cancer, reaching 7.2%. The correlation analysis between MSI and TMB was performed on patients of various cancer types. The results showed that: in each cancer type, MSI-H patients had TMB greater than 10, and 26.83% of MSI-H patients had TMB greater than 100 in colorectal cancer patients. The result of correlation analysis showed that there was no significant correlation between the patient's age and the risk of MSI mutation ( P> 0.05). In addition to PAAD and LUAD, the expression of PD-L1 in MSI-H patients was higher than that in MSS patients in other cancer types( P< 0.05). The correlation analysis between PD-L1 expression and TMB in patients found that in colorectal cancer, the higher the expression of PD-L1, the higher the patient's TMB ( P< 0.05). Conclusions: In this study, we explored the incidence of MSI-H in pan-cancer patients in China and found that the TMB was greater than 10 in patients with MSI-H. Compared with MSS patients, MSI-H patients have higher PD-L1 expression, and the higher the PD-L1 expression in colorectal cancer, the higher the TMB value of patients.

Exploration of the TMB and hypermutation landscape in Chinese pan-cancer patient by next-generation sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14575-e14575
Author(s):  
Shuo Wang ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Age And Gender ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cancer Types ◽  
And Gender ◽  
Chinese Cancer Patients ◽  
Pan Cancer ◽  
Generation Sequencing

e14575 Background: Among a variety of malignant tumors, the level of the patient's TMB was currently an important criterion for clinical judgment whether to adopt immunotherapy. Hypermutation could produce many nearby mutation sites at the same time, which seriously damages genetic material and may cause cancer. Therefore, performing TMB detection on cancer patients and understanding the occurrence of hypermutation in pan-cancer patients will help clinical researchers to further understand the disease characteristics of cancer patients and helped the choice of treatment methods. Previously, TMB and Hypermutation had been tested and studied in pan-cancer patients in the United States and Europe, but rare research was reported in China. In this study, we explored the TMB and hypermutation landscape in Chinese pan-cancer patient by next-generation sequencing. Methods: A total of 8,361 cancer patients from multiple cancer hospitals and research centers in China were included in the study. We sequenced 8,361 Chinese cancer patients from 8 cancer types using the oncopanscan product of Genetron Health Co., Ltd. and calculated the tumor mutation burden of the patients. We separately analyzed the tumor mutation burden of patients in 8 cancer types and analyzed the relationship between the occurrence of hypermutation and the patient's age and gender. Results: The results showed that in pan-cancer, hypermutation patients accounted for 16.97%, and ultrahypermutation patients accounted for 0.78%. Among them, patients with lung cancer have the highest proportion of hypermutation, reaching 27.72%, and patients with colorectal cancer have the highest proportion of ultrahypermutation, reaching 2.86%. Correlation analysis between TMB and age and gender was carried out on 8336 patients. The results showed that in the patients with intrahepatic bile duct cancer, the proportion of men and women was the same. Among the other cancer types, hypermutation patients were more male, and the proportion of men with liver cancer was the largest, with 90 percent. We further explored the correlation between the TMB of pan-cancer patients and the patient’s age, and found that in gastric cancer, liver cancer, and melanoma, the older patients have higher TMB; however, the younger the patients in brain cancer, the higher the TMB ( P<0.05). Conclusions: In this study, we explored the TMB and hypermutation landscape in Chinese pan-Cancer patient for the first time. We found that among Chinese cancer patients, lung cancer patients have the highest proportion of hypermutation. In a variety of cancers, hypermutation patients account for a higher proportion of men, and the older the patient, the higher the TMB.

An ultrasensitive method for noninvasive pan-cancer early detection based on targeted methylation sequencing of cell-free DNA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10544-10544
Author(s):  
Tiancheng Han ◽  
Yuanyuan Hong ◽  
Pei Zhihua ◽  
Song Xiaofeng ◽  
Jianing Yu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Detection ◽  
Real World ◽  
Early Stage ◽  
Validation Dataset ◽  
Cpg Sites ◽  
Free Dna ◽  
Cancer Types ◽  
Discovery Dataset ◽  
Pan Cancer

10544 Background: Screening the biomarkers from the cell-free DNA (cfDNA) of peripheral blood is a non-invasive and promising method for cancer diagnosis. Among diverse types of biomarkers, epigenetic biomarkers have been reported to be one of the most promising ones. Epigenetic modifications are widespread on the human genome and generally have strong signals due to the similar methylation patterns shared by adjacent CpG sites. Although some epigenetic diagnostic methods have been developed based on cfDNAs, few of them could be applied to pan-cancer and their sensitivities are barely satisfactory for early cancer detection. Methods: Targeted methylation sequencing was performed using our in-house-designed panel targeting regions with abundant cancer-specific methylation CpGs. The cfDNA samples from 80 healthy individuals and 549 cancer patients of 14 cancer types were separately sequenced. The dataset was randomly split into one discovery dataset and one validation dataset. Moreover, cfDNA samples from four cancer patients were diluted with the healthy cfDNAs to generate 12 in vitro simulated samples with low circulating tumor DNA (ctDNA) fraction. Additionally, DNAs extracted from 130 unmatched tumor formalin fixation and paraffin embedding (FFPE) samples of 10 cancer types were sequenced to screen the diagnostic biomarkers. Adjacent CpG sites were first merged into methylation-correlated blocks (MCB) according to their correlations of methylation levels in tumor DNAs. The MCBs with higher methylation levels in tumor DNAs than that of healthy cfDNAs (from the discovery dataset) were defined as our hypermethylation biomarkers. For each cfDNA sample, a hypermethylation score (HM-score) was computed to measure the overall methylation level difference of selected biomarkers. The performance of our method was evaluated with the real-world dataset, while the limit of detection was estimated using the simulated low-ctDNA samples. Results: Our model based on 37 hypermethylation MCB biomarkers achieved an area under the curve (AUC) of 0.89 and 0.86 in the real-world pan-cancer discovery and validation cfDNA datasets, respectively. Furthermore, the overall specificity and sensitivity are 100% and 76.19% in the discovery dataset, and 96.67% and 72.86% in the validation dataset. In the validation dataset, 28/40 (70%) of early-stage colorectal cancer patients and 10/20 (50%) of non-small-cell lung cancer patients were successfully diagnosed. Additionally, all the simulated samples with theoretical ctDNA factions over 0.5% were predicted as diseased, demonstrating the ability of our method to detect tumor signals at early stages. Conclusions: Our cfDNA-based epigenetic method outperforms currently available methods in various cancer types, and is promising to be applied to early-stage cancer detection and samples with low ctDNA fractions.

scholarly journals Karakteristik Klinikopatologik Pasien Kanker Payudara dengan Metastasis Tulang di RSUP Sanglah pada Tahun 2014 - 2018

e-CliniC ◽  
2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Putu Krishna B. S. Putra ◽  
I Wayan J. Sumadi ◽  
Ni Putu Sriwidyani ◽  
IG Budhi Setiawan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Invasive Carcinoma ◽  
Molecular Subtype ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Luminal B ◽  
Histopathological Type

Abstract: Breast cancer is the most common cancer in woman. Metastasis often occurs especially to the bones. This study was aimed to determine the characteristics of breast cancer patients with bone metastasis. This was a descriptive study with a cross-sectional design. Samples were 46 breast cancer patients with bone metastasis recorded at Sanglah Hospital from 2014 until 2018. Data of pathological examination archives of Oncology Surgery Division Medical Faculty of Udayana University/Sanglah General Hospital were used to obtain the clinicopathological characteristics of metastatic breast cancer patients based on age, lateralization, histopathological type, and tumor molecular subtype. The results showed that most cases of metastatic breast cancer were aged 40-49 years as many 21 patients (45.7%), minimal difference in lateralization between right breast as many 22 patients (47.8%) and left breast 23 patients (50%). The most common histopathological type was invasive carcinoma of no special type as many 34 patients (73.9%). The most common tumor subtype was the luminal B subtype as many 21 patients (45.7%). In conclusion, most patients of breast cancer with bone metastasis were 40-49 years old, invasive carcinoma of no special type, molecular subtype of luminal B, and no significant difference between lateralization to the right and left breast.Keywords: breast cancer, bone, metastasis, clinicopathological caharacteristics Abstrak: Kanker payudara merupakan jenis kanker yang paling sering dijumpai pada wanita. Metastasis sering terjadi terutama pada tulang. Penelitian ini bertujuan untuk mengetahui karakteristik pasien kanker payudara dengan metastasis tulang di RSUP Sanglah Denpasar. Jenis penelitian ialah deskriptif dengan desain potong lintang. Sampel penelitian ialah 46 pasien kanker payudara dengan metastasis tulang yang tercatat di RSUP Sanglah tahun 2014-2018. Data diambil dari arsip hasil pemeriksaan patologi di Subdivisi Bedah Onkologi, Departemen/Kelompok Staf Medis (KSM) Bedah Fakultas Kedokteran Universitas Udayana (FK UNUD)/RSUP Sanglah untuk mendapatkan karakteristik klinikopatologi pasien kanker payudara metastasis tulang berdasarkan usia, lateralisasi, tipe histopatologik, dan subtipe molekuler tumor. Hasil penelitian menunjukkan kasus terbanyak terjadi pada rentang usia 40-49 tahun sebanyak 21 orang (45,7%), dengan lateralisasi tidak jauh berbeda antara payudara kanan sebanyak 22 orang (47,8) dan kiri sebanyak 23 orang (50%). Tipe histopatologik yang lebih sering ditemukan yaitu invasive carcinoma of no special type sebanyak 34 orang (73,9%). Subtipe molekuler yang paling banyak ditemukan ialah subtipe luminal B sebanyak 21 orang (45,7%). Simpulan penelitian ini pasien kanker payudara dengan metastasis tulang berada pada rentang usia 40-49 tahun, invasive carcinoma of no special type, subtipe molekuler luminal B. dan lateralisasi payudara kanan dan kiri tidak jauh berbeda.Kata kunci: kanker payudara, metastasis, tulang, karakteristik klinikopatologik

scholarly journals VPS52 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Free Survival ◽  
Significant Gene ◽  
Vacuolar Protein

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of vacuolar protein sorting 52, encoded by VPS52 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, VPS52 expression was correlated with recurrence-free survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. VPS52 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals MAP4K2 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Mitogen Activated Protein Kinase ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Mitogen Activated Protein ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of mitogen-activated protein kinase kinase kinase kinase 2, encoded by MAP4K2 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, MAP4K2 expression was correlated with distant metastasis-free survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. MAP4K2 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals PAX5 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of paired box 5, encoded by PAX5 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, PAX5 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. PAX5 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals GBP5 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Significant Gene ◽  
Inflammasome Component ◽  
Guanylate Binding Protein

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival at time of analysis: dead or alive. The inflammasome component and guanylate-binding protein GBP5 emerged as among the most significant differences, transcriptome-wide, when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, GBP5 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. GBP5 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals PD-L2 (PDCD1LG2) expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Programmed Cell Death 1 ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of programmed cell death 1 ligand 2, encoded by PDCD1LG2, also known as PD-L2, when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, PD-L2 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. PD-L2 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals HES1 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Hes1 Expression ◽  
Significant Gene ◽  
Enhancer Of Split

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of hairy and enhancer of split 1, encoded by HES1 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, HES1 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. HES1 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

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