Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow

Authors: Glenn Deng, Sujatha Krishnakumar, Ashley A Powell, Haiyu Zhang, Michael N Mindrinos, Melinda L Telli, Ronald W Davis, Stefanie S Jeffrey

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

Therapeutic decisions in cancer are generally guided by molecular biomarkers or, for some newer therapeutics, primary tumor genotype. However, because biomarkers or genotypes may change as new metastases emerge, circulating tumor cells (CTCs) from blood are being investigated for a role in guiding real-time drug selection during disease progression, expecting that CTCs will comprehensively represent the full spectrum of genomic changes in metastases. However, information is limited regarding mutational heterogeneity among CTCs and metastases in breast cancer as discerned by single cell analysis. The presence of disseminated tumor cells (DTCs) in bone marrow also carry prognostic significance in breast cancer, but with variability between CTC and DTC detection. Here we analyze a series of single tumor cells, CTCs, and DTCs for PIK3CA mutations and report CTC and corresponding metastatic genotypes.

Methods

We used the MagSweeper, an immunomagnetic separation device, to capture live single tumor cells from breast cancer patients’ primary and metastatic tissues, blood, and bone marrow. Single cells were screened for mutations in exons 9 and 20 of the PIK3CA gene. Captured DTCs grown in cell culture were also sequenced for PIK3CA mutations.

Results

Among 242 individual tumor cells isolated from 17 patients and tested for mutations, 48 mutated tumor cells were identified in three patients. Single cell analyses revealed mutational heterogeneity among CTCs and tumor cells in tissues. In a patient followed serially, there was mutational discordance between CTCs, DTCs, and metastases, and among CTCs isolated at different time points. DTCs from this patient propagated in vitro contained a PIK3CA mutation, which was maintained despite morphological changes during 21 days of cell culture.

Conclusions

Single cell analysis of CTCs can demonstrate genotypic heterogeneity, changes over time, and discordance from DTCs and distant metastases. We present a cautionary case showing that CTCs from any single blood draw do not always reflect metastatic genotype, and that CTC and DTC analyses may provide independent clinical information. Isolated DTCs remain viable and can be propagated in culture while maintaining their original mutational status, potentially serving as a future resource for investigating new drug therapies.
Appendix
Available only for authorised users
Literature
1.
Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, Furet P, Gao H, Ferretti S, Wang Y, Trappe J, Brachmann SM, Maira SM, Wilson CJ, Boehm M, Garcia-Echeverria C, Chene P, Wiesmann M, Cozens R, Lehar J, Schlegel R, Caravatti G, Hofmann F, Sellers WR: Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014, 13: 1117-1129.CrossRefPubMed
2.
Janku F, Hong DS, Fu S, Piha-Paul SA, Naing A, Falchook GS, Tsimberidou AM, Stepanek VM, Moulder SL, Lee JJ, Luthra R, Zinner RG, Broaddus RR, Wheler JJ, Kurzrock R: Assessing PIK3CA and PTEN in Early-Phase Trials with PI3K/AKT/mTOR Inhibitors. Cell Rep. 2014, 6: 377-387.CrossRefPubMedPubMedCentral
3.
Patel SP, Lazar AJ, Papadopoulos NE, Liu P, Infante JR, Glass MR, Vaughn CS, LoRusso PM, Cohen RB, Davies MA, Kim KB: Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma. Cancer. 2013, 119: 799-805.CrossRefPubMed
4.
Pao W, Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011, 12: 175-180.CrossRefPubMed
5.
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, et al: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010, 11: 753-762.CrossRefPubMed
6.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012, 366: 883-892.CrossRefPubMedPubMedCentral
7.
Dupont Jensen J, Laenkholm AV, Knoop A, Ewertz M, Bandaru R, Liu W, Hackl W, Barrett JC, Gardner H: PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res. 2011, 17: 667-677.CrossRefPubMed
8.
9.
Jeselsohn R, Yelensky R, Buchwalter G, Frampton GM, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo A, Cristofanilli M, Gomez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross J, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt SJ, Come SE, Pusztai L, Stephens PJ, Brown M, Miller VA: Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor positive breast cancer. Clin Cancer Res. 2014, 20: 1757-1767.CrossRefPubMedPubMedCentral
10.
Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor GA, Teschendorff AE, Tse K, Turashvili G, Varhol R, Warren RL, Watson P, Zhao Y, Caldas C, Huntsman D, Hirst M, Marra MA, Aparicio S: Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009, 461: 809-813.CrossRefPubMed
11.
12.
Pantel K, Alix-Panabières C: Real-time liquid biopsy in cancer patients: fact or fiction?. Cancer Res. 2013, 73: 6384-6388.CrossRefPubMed
13.
Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM, Lax S, Waldispuehl-Geigl J, Mauermann O, Lackner C, Höfler G, Eisner F, Sill H, Samonigg H, Pantel K, Riethdorf S, Bauernhofer T, Geigl JB, Speicher MR: Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res. 2013, 73: 2965-2975.CrossRefPubMed
14.
Banys M, Krawczyk N, Fehm T: The role and clinical relevance of disseminated tumor cells in breast cancer. Cancers (Basel). 2014, 6: 143-152.CrossRef
15.
Møller EK, Kumar P, Voet T, Peterson A, Van Loo P, Mathiesen RR, Fjelldal R, Grundstad J, Borgen E, Baumbusch LO, Naume B, Børresen-Dale AL, White KP, Nord S, Kristensen VN: Next-generation sequencing of disseminated tumor cells. Front Oncol. 2013, 3: 320-CrossRefPubMedPubMedCentral
16.
Mathiesen RR, Fjelldal R, Liestøl K, Due EU, Geigl JB, Riethdorf S, Borgen E, Rye IH, Schneider IJ, Obenauf AC, Mauermann O, Nilsen G, Christian Lingjaerde O, Børresen-Dale AL, Pantel K, Speicher MR, Naume B, Baumbusch LO: High-resolution analyses of copy number changes in disseminated tumor cells of patients with breast cancer. Int J Cancer. 2012, 131: E405-E415.CrossRefPubMed
17.
Solakoglu O, Maierhofer C, Lahr G, Breit E, Scheunemann P, Heumos I, Pichlmeier U, Schlimok G, Oberneder R, Kollermann MW, Kollermann J, Speicher MR, Pantel K: Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors. Proc Natl Acad Sci U S A. 2002, 99: 2246-2251.CrossRefPubMedPubMedCentral
18.
19.
Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W, Xiao W, Davis MM, Pease RF, Mindrinos MN, Jeffrey SS, Davis RW: Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci U S A. 2009, 106: 3970-3975.CrossRefPubMedPubMedCentral
20.
Ameri K, Luong R, Zhang H, Powell AA, Montgomery KD, Espinosa I, Bouley DM, Harris AL, Jeffrey SS: Circulating tumour cells demonstrate an altered response to hypoxia and an aggressive phenotype. Br J Cancer. 2010, 102: 561-569.CrossRefPubMedPubMedCentral
21.
Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, Telli ML, Advani RH, Carlson RW, Mollick JA, Sheth S, Kurian AW, Ford JM, Stockdale FE, Quake SR, Pease RF, Mindrinos MN, Bhanot G, Dairkee SH, Davis RW, Jeffrey SS: Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PloS One. 2012, 7: e33788-CrossRefPubMedPubMedCentral
22.
Network CGA: Comprehensive molecular portraits of human breast tumours. Nature. 2012, 490: 61-70.CrossRef
23.
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT: An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008, 68: 6084-6091.CrossRefPubMedPubMedCentral
24.
Kalinsky K, Jacks LM, Heguy A, Patil S, Drobnjak M, Bhanot UK, Hedvat CV, Traina TA, Solit D, Gerald W, Moynahan ME:2: PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res. 2009, 15: 5049-5059.CrossRefPubMed
25.
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE: High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004, 304: 554-CrossRefPubMed
26.
Deng G, Herrler M, Burgess D, Manna E, Krag D, Burke JF: Enrichment with anticytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients. Breast Cancer Res. 2008, 10: R69-CrossRefPubMedPubMedCentral
27.
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004, 351: 781-791.CrossRefPubMed
28.
Braun S, Pantel K, Müller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmüller G, Schlimok G: Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000, 342: 525-533.CrossRefPubMed
29.
Liang X, Lau QC, Salto-Tellez M, Putti TC, Loh M, Sukumar S: Mutational hotspot in exon 20 of PIK3CA in breast cancer among Singapore Chinese. Cancer Biol Ther. 2006, 5: 544-548.CrossRefPubMed
30.
Higgins MJ, Jelovac D, Barnathan E, Blair B, Slater S, Powers P, Zorzi J, Jeter SC, Oliver GR, Fetting J, Emens L, Riley C, Stearns V, Diehl F, Angenendt P, Huang P, Cope L, Argani P, Murphy KM, Bachman KE, Greshock J, Wolff AC, Park BH: Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood. Clin Cancer Res. 2012, 18: 3462-3469.CrossRefPubMedPubMedCentral
31.
Hollestelle A, Elstrodt F, Nagel JH, Kallemeijn WW, Schutte M: Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines. Mol Cancer Res. 2007, 5: 195-201.CrossRefPubMed
32.
Kataoka Y, Mukohara T, Shimada H, Saijo N, Hirai M, Minami H: Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines. Ann Oncol. 2010, 21: 255-262.CrossRefPubMed
33.
Wu G, Xing M, Mambo E, Huang X, Liu J, Guo Z, Chatterjee A, Goldenberg D, Gollin SM, Sukumar S, Trink B, Sidransky D: Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res. 2005, 7: R609-CrossRefPubMedPubMedCentral
34.
Muller CI, Miller CW, Hofmann WK, Gross ME, Walsh CS, Kawamata N, Luong QT, Koeffler HP: Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene. Leukemia Res. 2007, 31: 27-32.CrossRef
35.
Bidard FC, Fehm T, Ignatiadis M, Smerage JB, Alix-Panabières C, Janni W, Messina C, Paoletti C, Müller V, Hayes DF, Piccart M, Pierga JY: Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials. Cancer Metastasis Rev. 2013, 32: 179-188.CrossRefPubMed
36.
Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O'Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF: Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol. 2014, Epub ahead of print
37.
Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S: Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013, 339: 580-584.CrossRefPubMedPubMedCentral
38.
Chen CL, Mahalingam D, Osmulski P, Jadhav RR, Wang CM, Leach RJ, Chang TC, Weitman SD, Kumar AP, Sun L, Gaczynska ME, Thompson IM, Huang TH: Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate. 2013, 73: 813-826.CrossRefPubMed
39.
Yokobori T, Iinuma H, Shimamura T, Imoto S, Sugimachi K, Ishii H, Iwatsuki M, Ota D, Ohkuma M, Iwaya T, Nishida N, Kogo R, Sudo T, Tanaka F, Shibata K, Toh H, Sato T, Barnard GF, Fukagawa T, Yamamoto S, Nakanishi H, Sasaki S, Miyano S, Watanabe T, Kuwano H, Mimori K, Pantel K, Mori M: Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res. 2013, 73: 2059-2069.CrossRefPubMed
40.
Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D, Goodman JC, Groves MD, Marchetti D: The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med. 2013, 5: 180ra48-Erratum in: Sci Transl Med 2013, 5:189er5CrossRefPubMed
41.
Di Nicolantonio F, Arena S, Tabernero J, Grosso S, Molinari F, Macarulla T, Russo M, Cancelliere C, Zecchin D, Mazzucchelli L, Sasazuki T, Shirasawa S, Geuna M, Frattini M, Baselga J, Gallicchio M, Biffo S, Bardelli A: Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. J Clin Invest. 2010, 120: 2858-2866.CrossRefPubMedPubMedCentral
42.
Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, Francis JM, Zhang CZ, Shalek AK, Satija R, Trombetta JJ, Lu D, Tallapragada N, Tahirova N, Kim S, Blumenstiel B, Sougnez C, Lowe A, Wong B, Auclair D, Van Allen EM, Nakabayashi M, Lis RT, Lee GS, Li T, Chabot MS, Ly A, Taplin ME, Clancy TE, Loda M, et al: Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol. 2014, 32: 479-484.CrossRefPubMedPubMedCentral
43.
Alix-Panabières C, Pantel K: Technologies for detection of circulating tumor cells: facts and vision. Lab Chip. 2014, 14: 57-62.CrossRefPubMed
44.
Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C: Molecular analysis of circulating tumour cells-biology and biomarkers. Nat Rev Clin Oncol. 2014, 11: 129-144.CrossRefPubMed
45.
Lowes LE, Allan AL: Recent advances in the molecular characterization of circulating tumor cells. Cancers (Basel). 2014, 6: 595-624.CrossRef
46.
Van Loo P, Voet T: Single cell analysis of cancer genomes. Curr Opin Genet Dev. 2014, 24C: 82-91.CrossRef
47.
Schneck H, Blassl C, Meier-Stiegen F, Neves RP, Janni W, Fehm T, Neubauer H: Analysing the mutational status of PIK3CA in circulating tumor cells from metastatic breast cancer patients. Mol Oncol. 2013, 7: 976-986.CrossRefPubMed
48.
Harb W, Fan A, Tran T, Danila DC, Keys D, Schwartz M, Ionescu-Zanetti C: Mutational analysis of circulating tumor cells using a novel microfluidic collection device and qPCR assay. Transl Oncol. 2013, 6: 528-538.CrossRefPubMedPubMedCentral
49.
Gutiérrez C, Rodriguez J, Patiño-García A, García-Foncillas J, Salgado J: KRAS mutational status analysis of peripheral blood isolated circulating tumor cells in metastatic colorectal patients. Oncol Lett. 2013, 6: 1343-1345.PubMedPubMedCentral
50.
Fabbri F, Carloni S, Zoli W, Ulivi P, Gallerani G, Fici P, Chiadini E, Passardi A, Frassineti GL, Ragazzini A, Amadori D: Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs. Cancer Lett. 2013, 335: 225-231.CrossRefPubMed
51.
Mostert B, Jiang Y, Sieuwerts AM, Wang H, Bolt-de Vries J, Biermann K, Kraan J, Lalmahomed Z, van Galen A, de Weerd V, van der Spoel P, Ramírez-Moreno R, Verhoef C, Ijzermans JN, Wang Y, Gratama JW, Foekens JA, Sleijfer S, Martens JW: KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue. Int J Cancer. 2013, 133: 130-141.CrossRefPubMed
52.
Tórtola S, Steinert R, Hantschick M, Peinado MA, Gastinger I, Stosiek P, Lippert H, Schlegel W, Reymond MA: Discordance between K-ras mutations in bone marrow micrometastases and the primary tumor in colorectal cancer. J Clin Oncol. 2001, 19: 2837-2843.PubMed
53.
Raimondi C, Nicolazzo C, Gradilone A, Giannini G, De Falco E, Chimenti I, Varriale E, Hauch S, Plappert L, Cortesi E, Gazzaniga P: Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer. Cancer Biol Ther. 2014, 15: 496-503.CrossRefPubMedPubMedCentral
54.
Klein CA, Seidl S, Petat-Dutter K, Offner S, Geigl JB, Schmidt-Kittler O, Wendler N, Passlick B, Huber RM, Schlimok G, Baeuerle PA, Riethmüller G: Combined transcriptome and genome analysis of single micrometastatic cells. Nat Biotechnol. 2002, 20: 387-392.CrossRefPubMed
55.
56.
Magbanua MJ, Sosa EV, Roy R, Eisenbud LE, Scott JH, Olshen A, Pinkel D, Rugo HS, Park JW: Genomic profiling of isolated circulating tumor cells from metastatic breast cancer patients. Cancer Res. 2013, 73: 30-40.CrossRefPubMed
57.
Gasch C, Bauernhofer T, Pichler M, Langer-Freitag S, Reeh M, Seifert AM, Mauermann O, Izbicki JR, Pantel K, Riethdorf S: Heterogeneity of epidermal growth factor receptor status and mutations of KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer. Clin Chem. 2013, 59: 252-260.CrossRefPubMed
58.
Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z, Zong C, Bai H, Chapman AR, Zhao J, Xu L, An T, Ma Q, Wang Y, Wu M, Sun Y, Wang S, Li Z, Yang X, Yong J, Su XD, Lu Y, Bai F, Xie XS, Wang J: Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci U S A. 2013, 110: 21083-21088.CrossRefPubMedPubMedCentral
59.
Sakaizawa K, Goto Y, Kiniwa Y, Uchiyama A, Harada K, Shimada S, Saida T, Ferrone S, Takata M, Uhara H, Okuyama R: Mutation analysis of BRAF and KIT in circulating melanoma cells at the single cell level. Br J Cancer. 2012, 106: 939-946.CrossRefPubMedPubMedCentral
60.
Ulmer A, Schmidt-Kittler O, Fischer J, Ellwanger U, Rassner G, Riethmüller G, Fierlbeck G, Klein CA: Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells. Clin Cancer Res. 2004, 10: 531-537.CrossRefPubMed
61.
Ross AA, Cooper BW, Lazarus HM, Mackay W, Moss TJ, Ciobanu N, Tallman MS, Kennedy MJ, Davidson NE, Sweet D, Winter C, Akard L, Jansen J, Copelan E, Meagher RC, Herzig RH, Klumpp TR, Kahn DG, Warner NE: Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques. Blood. 1993, 82: 2605-2610.PubMed
Metadata
Title
Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow
Authors
Glenn Deng
Sujatha Krishnakumar
Ashley A Powell
Haiyu Zhang
Michael N Mindrinos
Melinda L Telli
Ronald W Davis
Stefanie S Jeffrey
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-456

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Myofibroblastic stromal reaction and lymph node status in invasive breast carcinoma: possible role of the TGF-β1/TGF-βR1 pathway

Research article

Study of the cytotoxicity of asiaticoside on rats and tumour cells

Study protocol

FOXFIRE protocol: an open-label, randomised, phase III trial of 5-fluorouracil, oxaliplatin and folinic acid (OxMdG) with or without interventional Selective Internal Radiation Therapy (SIRT) as first-line treatment for patients with unresectable liver-only or liver-dominant metastatic colorectal cancer

Research article

The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma

Erratum

Erratum to: Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer

Research article

1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits