Development of personalized tumor biomarkers using massively parallel sequencing.

Abstract:

:Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers with massively parallel sequencing revealed an average of nine rearranged sequences (range, 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints was able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.

journal_name

Sci Transl Med

authors

Leary RJ,Kinde I,Diehl F,Schmidt K,Clouser C,Duncan C,Antipova A,Lee C,McKernan K,De La Vega FM,Kinzler KW,Vogelstein B,Diaz LA Jr,Velculescu VE

doi

10.1126/scitranslmed.3000702

subject

Has Abstract

pub_date

2010-02-24 00:00:00

pages

20ra14

issue

20

eissn

1946-6234

issn

1946-6242

pii

2/20/20ra14

journal_volume

2

pub_type

杂志文章
  • The fate and toxicity of Raman-active silica-gold nanoparticles in mice.

    abstract::Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak natu...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3001963

    authors: Thakor AS,Luong R,Paulmurugan R,Lin FI,Kempen P,Zavaleta C,Chu P,Massoud TF,Sinclair R,Gambhir SS

    更新日期:2011-04-20 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract::Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000522

    authors: Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期:2010-04-21 00:00:00

  • Serotonergic neurons mediate dyskinesia side effects in Parkinson's patients with neural transplants.

    abstract::Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and i...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000976

    authors: Politis M,Wu K,Loane C,Quinn NP,Brooks DJ,Rehncrona S,Bjorklund A,Lindvall O,Piccini P

    更新日期:2010-06-30 00:00:00

  • miRNA processing and human cancer: DICER1 cuts the mustard.

    abstract::Numerous studies have implicated microRNAs (miRNAs) in cancer initiation and progression. In contrast, only recently has attention been focused on the pathway that generates these regulatory molecules. The identification of neoplasia-associated germline mutations in DICER1 has focused translational research on compone...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3002493

    authors: Bahubeshi A,Tischkowitz M,Foulkes WD

    更新日期:2011-11-30 00:00:00

  • A vitamin to D-crease sunburn.

    abstract::High doses of oral vitamin D3 attenuate skin inflammation following experimentally induced sun damage. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aan5233

    authors: Scharschmidt TC

    更新日期:2017-06-14 00:00:00

  • Turning back the clock.

    abstract::Increased DNA breaks in aging skeletal muscle activate the DNA-PK pathway, whereas blocking this pathway improves mitochondrial density, physical fitness, body weight, and insulin resistance in mice. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aan4290

    authors: Shoemaker AH

    更新日期:2017-05-17 00:00:00

  • Molecular profiling: moving away from tumor philately.

    abstract::Despite the remarkable enhancements in breast cancer classification and characterization, an exhaustive comprehension of the underlying carcinogenic processes and an accurate prediction of its clinical behavior are yet to be achieved. On the wave of recent scientific advances and clinical findings, new cutting-edge te...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3001329

    authors: Reis-Filho JS,Weigelt B,Fumagalli D,Sotiriou C

    更新日期:2010-09-01 00:00:00

  • GABA neurons in the nucleus tractus solitarius express GLP-1 receptors and mediate anorectic effects of liraglutide in rats.

    abstract::The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aay8071

    authors: Fortin SM,Lipsky RK,Lhamo R,Chen J,Kim E,Borner T,Schmidt HD,Hayes MR

    更新日期:2020-03-04 00:00:00

  • Whole-genome sequencing for optimized patient management.

    abstract::Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inherita...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002243

    authors: Bainbridge MN,Wiszniewski W,Murdock DR,Friedman J,Gonzaga-Jauregui C,Newsham I,Reid JG,Fink JK,Morgan MB,Gingras MC,Muzny DM,Hoang LD,Yousaf S,Lupski JR,Gibbs RA

    更新日期:2011-06-15 00:00:00

  • Vaccination of dogs in an African city interrupts rabies transmission and reduces human exposure.

    abstract::Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N'Djaména, as previously published. We developed a determi...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaf6984

    authors: Zinsstag J,Lechenne M,Laager M,Mindekem R,Naïssengar S,Oussiguéré A,Bidjeh K,Rives G,Tessier J,Madjaninan S,Ouagal M,Moto DD,Alfaroukh IO,Muthiani Y,Traoré A,Hattendorf J,Lepelletier A,Kergoat L,Bourhy H,Dacheux L,

    更新日期:2017-12-20 00:00:00

  • Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment.

    abstract::Cancer immunotherapy using antibodies that target immune checkpoints has delivered outstanding results. However, responses only occur in a subset of patients, and it is not fully understood what biological processes determine an effective outcome. This lack of understanding hinders the development of rational combinat...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aav7816

    authors: Zemek RM,De Jong E,Chin WL,Schuster IS,Fear VS,Casey TH,Forbes C,Dart SJ,Leslie C,Zaitouny A,Small M,Boon L,Forrest ARR,Muiri DO,Degli-Esposti MA,Millward MJ,Nowak AK,Lassmann T,Bosco A,Lake RA,Lesterhuis WJ

    更新日期:2019-07-17 00:00:00

  • Recapitulating bone development through engineered mesenchymal condensations and mechanical cues for tissue regeneration.

    abstract::Large bone defects cannot form a callus and exhibit high complication rates even with the best treatment strategies available. Tissue engineering approaches often use scaffolds designed to match the properties of mature bone. However, natural fracture healing is most efficient when it recapitulates development, formin...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aav7756

    authors: McDermott AM,Herberg S,Mason DE,Collins JM,Pearson HB,Dawahare JH,Tang R,Patwa AN,Grinstaff MW,Kelly DJ,Alsberg E,Boerckel JD

    更新日期:2019-06-05 00:00:00

  • Complexity in common diseases: big biology for all.

    abstract::The Commentary of Mills and Sykes in Science Translational Medicine presented their thesis on the advent of high-throughput technologies and the dangers they may represent for the future of biomedical research. In response, we argue that true progress on the diagnosis and treatment of common human diseases will requir...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.3000882

    authors: Lamb JR,Gibson NW

    更新日期:2010-03-31 00:00:00

  • Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder.

    abstract::A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heteroto...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3005271

    authors: Parker WE,Orlova KA,Parker WH,Birnbaum JF,Krymskaya VP,Goncharov DA,Baybis M,Helfferich J,Okochi K,Strauss KA,Crino PB

    更新日期:2013-04-24 00:00:00

  • Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.

    abstract::A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aai7514

    authors: Bonsignori M,Kreider EF,Fera D,Meyerhoff RR,Bradley T,Wiehe K,Alam SM,Aussedat B,Walkowicz WE,Hwang KK,Saunders KO,Zhang R,Gladden MA,Monroe A,Kumar A,Xia SM,Cooper M,Louder MK,McKee K,Bailer RT,Pier BW,Jette CA

    更新日期:2017-03-15 00:00:00

  • Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy.

    abstract::Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac arrhythmias. To elucidate the underlying mechanisms and discover potential chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte-specific expression of the human 2057del2 mutation in the gene encoding plakoglobin. A high-th...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008008

    authors: Asimaki A,Kapoor S,Plovie E,Karin Arndt A,Adams E,Liu Z,James CA,Judge DP,Calkins H,Churko J,Wu JC,MacRae CA,Kléber AG,Saffitz JE

    更新日期:2014-06-11 00:00:00

  • Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis.

    abstract::Macrophages in the healthy intestine are highly specialized and usually respond to the gut microbiota without provoking an inflammatory response. A breakdown in this tolerance leads to inflammatory bowel disease (IBD), but the mechanisms by which intestinal macrophages normally become conditioned to promote microbial ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aao4755

    authors: Scott NA,Andrusaite A,Andersen P,Lawson M,Alcon-Giner C,Leclaire C,Caim S,Le Gall G,Shaw T,Connolly JPR,Roe AJ,Wessel H,Bravo-Blas A,Thomson CA,Kästele V,Wang P,Peterson DA,Bancroft A,Li X,Grencis R,Mowat AM,Hal

    更新日期:2018-10-24 00:00:00

  • Forty-year journey of angiogenesis translational research.

    abstract::Forty years ago, Judah Folkman predicted that tumor growth is dependent on angiogenesis and that inhibiting this process might be a new strategy for cancer therapy. This hypothesis formed the foundation of a new field of research that represents an excellent example of how a groundbreaking scientific discovery can be ...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3003149

    authors: Cao Y,Arbiser J,D'Amato RJ,D'Amore PA,Ingber DE,Kerbel R,Klagsbrun M,Lim S,Moses MA,Zetter B,Dvorak H,Langer R

    更新日期:2011-12-21 00:00:00

  • Clinical trial design: The nobility of randomization.

    abstract::A clinical trial evaluating HIV vaccine therapy teaches us much about optimal design (Sneller et al, this issue). ...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aaq0810

    authors: Michael NL

    更新日期:2017-12-06 00:00:00

  • How to handle an industry in disruption: Intervene or laissez-faire?

    abstract::An analysis of four regions in four countries suggests that the best way to mitigate disruption of the pharmaceutical industry is not to ignore or stem it but to sponsor initiatives that keep scientists engaged. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aaa3679

    authors: Munos B

    更新日期:2015-05-06 00:00:00

  • Hypercapnia increases airway smooth muscle contractility via caspase-7-mediated miR-133a-RhoA signaling.

    abstract::The elevation of carbon dioxide (CO2) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aat1662

    authors: Shigemura M,Lecuona E,Angulo M,Homma T,Rodríguez DA,Gonzalez-Gonzalez FJ,Welch LC,Amarelle L,Kim SJ,Kaminski N,Budinger GRS,Solway J,Sznajder JI

    更新日期:2018-09-05 00:00:00

  • Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice.

    abstract::Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as al...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aas9164

    authors: Reyes NJ,Yu C,Mathew R,Kunnen CM,Kalnitsky J,Redfern RL,Leonardi A,Perez VL,MacLeod AS,Gupta PK,Saban DR

    更新日期:2018-07-25 00:00:00

  • Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis.

    abstract::In multiple sclerosis (MS), lymphocyte--in particular B cell--transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which s...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008930

    authors: Palanichamy A,Apeltsin L,Kuo TC,Sirota M,Wang S,Pitts SJ,Sundar PD,Telman D,Zhao LZ,Derstine M,Abounasr A,Hauser SL,von Büdingen HC

    更新日期:2014-08-06 00:00:00

  • Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity.

    abstract::Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used sev...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002573

    authors: Navina S,Acharya C,DeLany JP,Orlichenko LS,Baty CJ,Shiva SS,Durgampudi C,Karlsson JM,Lee K,Bae KT,Furlan A,Behari J,Liu S,McHale T,Nichols L,Papachristou GI,Yadav D,Singh VP

    更新日期:2011-11-02 00:00:00

  • Getting to the root of hydrocephalus.

    abstract::The blood-borne lipid lysophosphatidic acid and its receptor contribute to fetal-onset hydrocephalus, a severe neurological disorder of newborns. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.3003119

    authors: McAllister JP

    更新日期:2011-09-07 00:00:00

  • CRISPR-enhanced engineering of therapy-sensitive cancer cells for self-targeting of primary and metastatic tumors.

    abstract::Tumor cells engineered to express therapeutic agents have shown promise to treat cancer. However, their potential to target cell surface receptors specific to the tumor site and their posttreatment fate have not been explored. We created therapeutic tumor cells expressing ligands specific to primary and recurrent tumo...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aao3240

    authors: Reinshagen C,Bhere D,Choi SH,Hutten S,Nesterenko I,Wakimoto H,Le Roux E,Rizvi A,Du W,Minicucci C,Shah K

    更新日期:2018-07-11 00:00:00

  • KLF6-SV1 drives breast cancer metastasis and is associated with poor survival.

    abstract::Metastasis is the major cause of cancer mortality. A more thorough understanding of the mechanisms driving this complex multistep process will aid in the identification and characterization of therapeutically targetable genetic drivers of disease progression. We demonstrate that KLF6-SV1, an oncogenic splice variant o...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3004688

    authors: Hatami R,Sieuwerts AM,Izadmehr S,Yao Z,Qiao RF,Papa L,Look MP,Smid M,Ohlssen J,Levine AC,Germain D,Burstein D,Kirschenbaum A,DiFeo A,Foekens JA,Narla G

    更新日期:2013-01-23 00:00:00

  • Estimating cholera incidence with cross-sectional serology.

    abstract::The development of new approaches to cholera control relies on an accurate understanding of cholera epidemiology. However, most information on cholera incidence lacks laboratory confirmation and instead relies on surveillance systems reporting medically attended acute watery diarrhea. If recent infections could be ide...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aau6242

    authors: Azman AS,Lessler J,Luquero FJ,Bhuiyan TR,Khan AI,Chowdhury F,Kabir A,Gurwith M,Weil AA,Harris JB,Calderwood SB,Ryan ET,Qadri F,Leung DT

    更新日期:2019-02-20 00:00:00

  • Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR.

    abstract::MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base pairing with 3' untranslated regions, primarily via seed sequences (nucleotides 2 to 8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequenc...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3006840

    authors: Rottiers V,Obad S,Petri A,McGarrah R,Lindholm MW,Black JC,Sinha S,Goody RJ,Lawrence MS,deLemos AS,Hansen HF,Whittaker S,Henry S,Brookes R,Najafi-Shoushtari SH,Chung RT,Whetstine JR,Gerszten RE,Kauppinen S,Näär AM

    更新日期:2013-11-20 00:00:00

  • Systemic AAV9.LAMP2B injection reverses metabolic and physiologic multiorgan dysfunction in a murine model of Danon disease.

    abstract::Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy associated with multiorgan dysfunction, including the heart, skeletal muscle, and liver. There are no specific treatments, and most male patients die from advanced heart failure during the second or third decade of life. DD is caused by mutations in th...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aax1744

    authors: Manso AM,Hashem SI,Nelson BC,Gault E,Soto-Hermida A,Villarruel E,Brambatti M,Bogomolovas J,Bushway PJ,Chen C,Battiprolu P,Keravala A,Schwartz JD,Shah G,Gu Y,Dalton ND,Hammond K,Peterson K,Saftig P,Adler ED

    更新日期:2020-03-18 00:00:00