A5003062527- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Chronic Lymphocytic Leukemia Research
- Mathematical Biology Tumor Growth
- Bladder and Urothelial Cancer Treatments
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Microtubule and mitosis dynamics
- Evolution and Genetic Dynamics
- Health, Environment, Cognitive Aging
- BRCA gene mutations in cancer
- Radiomics and Machine Learning in Medical Imaging
- Ovarian cancer diagnosis and treatment
- Urinary and Genital Oncology Studies
- Cancer, Lipids, and Metabolism
- Colorectal Cancer Surgical Treatments
- Liver Disease Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pancreatitis Pathology and Treatment
City of Hope
2022-2025
Translational Genomics Research Institute
2022-2025
Beckman Research Institute
2023-2025
Igenbio (United States)
2024-2025
Johns Hopkins University
2015-2024
Sidney Kimmel Comprehensive Cancer Center
2013-2024
Johns Hopkins Medicine
2015-2024
Seoul National University
2024
City Of Hope National Medical Center
2023
Sidney Kimmel Cancer Center
2014-2021
Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common types through assessment of the levels circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, 1005 patients with nonmetastatic, clinically detected cancers ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive median 70% types. The sensitivities ranged from 69 98% for five (ovary, esophagus)...
Crunching the numbers to explain cancer Why do some tissues give rise in humans a million times more frequently than others? Tomasetti and Vogelstein conclude that these differences can be explained by number of stem cell divisions. By plotting lifetime incidence various cancers against estimated normal divisions corresponding over lifetime, they found strong correlation extending five orders magnitude. This suggests random errors occurring during DNA replication cells are major contributing...
Detection of circulating tumor DNA in patients with resected stage II colon cancer provides evidence residual disease.
A substantial fraction of mutations in human cancer are attributable to random errors occurring during DNA replication.
The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. presence circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence a low risk recurrence. benefit for ctDNA-positive patients is not well understood.
Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% reproductive-age women can cause pelvic pain infertility. Endometriotic lesions are considered to be benign inflammatory but have cancerlike features such local invasion resistance apoptosis.
Adjuvant chemotherapy in patients with stage III colon cancer prevents recurrence by eradicating minimal residual disease. However, which remain at high risk of after completing standard adjuvant treatment cannot currently be determined. Postsurgical circulating tumor DNA (ctDNA) analysis can detect disease and is associated colorectal cancers.To determine whether serial postsurgical postchemotherapy ctDNA could provide a real-time indication therapy efficacy cancer.This multicenter,...
Significance Few patients with pancreatic cancer survive longer than 5 y, in part because most are identified only after their disease has progressed to an advanced stage. In this study, we show how combining mutations circulating tumor DNA (ctDNA) protein markers can result a screening test improved sensitivity while retaining specificity. The combination of the ctDNA and was superior any single marker. Moreover, detected nearly two-thirds cancers that had no evidence distant metastasis at...
A real-time trial of a cancer blood test Cancers diagnosed early are often more responsive to treatment. Blood tests that detect molecular markers have successfully identified individuals already known the disease. Lennon et al. conducted an exploratory study closely reflects way in which such would be used future. They evaluated feasibility and safety incorporating multicancer into routine clinical care 10,000 women with no history cancer. Over 12-month period, detected 26 cancers different...
Although it has been hypothesized that some of the somatic mutations found in tumors may occur before tumor initiation, there is little experimental or conceptual data on this topic. To gain insights into fundamental issue, we formulated a mathematical model for evolution which all relevant phases tissue’s history are considered. The makes prediction, validated by our empirical findings, number self-renewing tissues positively correlated with age patient at diagnosis. Importantly, analysis...
Significance The number of driver events required for human tumorigenesis has remained one the fundamental issues in cancer research since seminal studies Armitage and Doll. This question become even more important with recent genome-wide sequencing cancer, whose major goal is identification genes responsible tumor initiation progression. By using a novel approach that combines conventional epidemiologic data, we show only three sequential mutations are to develop lung colon adenocarcinomas,...
For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in LARC.We enrolled LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery. Somatic mutations individual patient's identified via massively parallel...
Significance While we age, our body accumulates random somatic mutations. These mutations spontaneously arise from endogenous and exogenous sources, such as DNA replication errors or environmental insults like smoking sunlight. Direct measurement of rare could help us understand the role in human aging, normal biology, disease processes. Here, develop bottleneck sequencing system (BotSeqS) a simple genome-wide sequencing-based method that accurately quantitates nuclear mitochondrial...
Endometrial and ovarian cancers can be detected through the analysis of DNA from Pap test fluids, intrauterine samples, plasma.
For patients with resected, nonmetastatic colorectal cancer (CRC), the optimal surveillance protocol remains unclear.To evaluate whether serial circulating tumor DNA (ctDNA) levels detected disease recurrence earlier, compared conventional postoperative surveillance, in resected CRC.This study included (n = 58) stage I, II, or III CRC who underwent radical surgical resection at 4 Swedish hospitals from February 2, 2007, to May 8, 2013. Eighteen received adjuvant chemotherapy discretion of...
Pancreatic cysts are common and often pose a management dilemma, because some precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop comprehensive test, CompCyst, guide the patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, cyst fluid genetic biochemical markers. Using data from 436 cysts, we trained CompCyst classify as those who required surgery,...
In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker minimal residual disease, is powerful prognostic factor in nonmetastatic cancer (CRC). Serial analysis ctDNA CRLM could inform optimal use perioperative chemotherapy. Here, we performed validation study confirm impact observed previous discovery study.We prospectively...
Cell-free DNA (cfDNA) concentrations from patients with cancer are often elevated compared those of healthy controls, but the sources this extra cfDNA have never been determined. To address issue, we assessed methylation patterns in 178 cancers colon, pancreas, lung, or ovary and 64 without cancer. Eighty-three these individuals had much greater than generally observed subjects. The major contributor all samples was leukocytes, accounting for ∼76% cfDNA, neutrophils predominating. This true...
Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk bladder cancer (BC), was positive 83% those who BC. Combined with cytology, detected 95% Of 56 upper tract cancer, 75% tested by UroSEEK, including 79% tumors. genetic...
The clonal relationship between ovarian high-grade serous carcinoma (HGSC) and its presumed precursor lesion, tubal intraepithelial (STIC), has been reported. However, when analyzing patients with concurrent the extensive tissues present at diagnosis may have effaced natural habitat of clone(s), obscuring tumor evolutionary history, or disseminated to anatomically adjacent fimbriae ends, masquerading as lesions. To circumvent these limitations, we analyzed genomic landscape incidental...
Abstract Studies in multiple solid tumor types have demonstrated the prognostic significance of ctDNA analysis after curative intent surgery. A combined data across completed studies could further our understanding circulating DNA (ctDNA) as a marker and inform future trial design. We individual patient from three independent cohort nonmetastatic colorectal cancer (CRC). Plasma samples were collected 4 to 10 weeks Mutations assayed using massively parallel sequencing technique called...
A new evaluation of previously published data suggested to us that the accumulation mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized normal stem cell division rates decrease test hypothesis, evaluated in epithelium human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant with contrast, did not colon aged mice, only small decreases were observed their intestine or...