{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:01:42Z","timestamp":1772139702649,"version":"3.50.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singhealth Surgery Academic Clinical Program","award":["the SingHealth Surgery ACP Surgeon-Scientist Strategic Start-up (S4G) Grant"],"award-info":[{"award-number":["the SingHealth Surgery ACP Surgeon-Scientist Strategic Start-up (S4G) Grant"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Known collectively as breast fibroepithelial lesions (FELs), the common fibroadenomas (FAs) and the rarer phyllodes tumors (PTs) are a heterogenous group of biphasic neoplasms. Owing to limited tissue availability, inter-observer variability, overlapping histological features and heterogeneity of these lesions, diagnosing them accurately on core biopsies is challenging. As the choice management option depends on the histological diagnosis; a novel 16-gene panel assay was developed to improve the accuracy of preoperative diagnosis on core biopsy specimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using this 16-gene panel, targeted amplicon-based sequencing was performed on 275 formalin-fixed, paraffin-embedded (FFPE) breast FEL specimens, archived at the Singapore General Hospital, from 2008 to 2012.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 167 FAs, 24 benign, 14 borderline and 6 malignant PTs, were profiled. Compared to FAs, PTs had significantly higher mutation rates in the<jats:italic>TERT<\/jats:italic>promoter (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009\u00a00.001),<jats:italic>RARA<\/jats:italic>(<jats:italic>p<\/jats:italic>\u2009&lt;\u2009\u00a00.001),<jats:italic>FLNA<\/jats:italic>,<jats:italic>RB1<\/jats:italic>and<jats:italic>TP53<\/jats:italic>(<jats:italic>p<\/jats:italic>\u2009=\u20090.002, 0.020 and 0.018, respectively). In addition to a higher mutational count (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009\u00a00.001),<jats:italic>TERT<\/jats:italic>promoter (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009\u00a00.001), frameshift, nonsense and splice site (<jats:italic>p<\/jats:italic>\u2009=\u20090.001, &lt;\u20090.001 and 0.043, respectively) mutations were also frequently observed in PTs.<\/jats:p><jats:p>A multivariate logistic regression model was built using these as variables and a predictive scoring system was developed. It classifies a FEL at low or high risk (score\u2009&lt;\u2009\u00a01 and\u2009\u2265\u20091, respectively) of being a PT. This scoring system has good discrimination (ROC area\u2009=\u20090.773, 95% CI: 0.70 to 0.85), calibration (<jats:italic>p<\/jats:italic>\u2009=\u20090.945) and is significant in predicting PTs (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This novel study demonstrates the ability to extract DNA of sufficient quality and quantity for targeted sequencing from FFPE breast core biopsy specimens, along with their successful characterization and profiling using our customized 16-gene panel. Prospective work includes validating the utility of this promising 16-gene panel assay as an adjunctive diagnostic tool in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12920-019-0588-2","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T13:15:06Z","timestamp":1571836506000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A novel genomic panel as an adjunctive diagnostic tool for the characterization and profiling of breast Fibroepithelial lesions"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-0455","authenticated-orcid":false,"given":"Yirong","family":"Sim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwendolene Xin Pei","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cedric Chuan Young","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikneswari","family":"Rajasegaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suet Far","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyong","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjanaa","family":"Nagarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai Yee","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aye Aye","family":"Thike","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey Chun Tatt","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nur Diyana Binte Md","family":"Nasir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronique Kiak Mien","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preetha","family":"Madhukumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Sean","family":"Yong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chow Yin","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benita Kiat Tee","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kong Wee","family":"Ong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin Tean","family":"Teh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puay Hoon","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"588_CR1","unstructured":"Eble JN, Tavassoli FA, Devilee P, Organization WH, Cancer IAfRo: pathology and genetics of Tumours of the breast and female genital organs: IARC press; 2003."},{"issue":"4","key":"588_CR2","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1177\/000313480006600408","volume":"66","author":"DP Geisler","year":"2000","unstructured":"Geisler DP, Boyle MJ, Malnar KF, McGee JM, Nolen MC, Fortner SM, Broughan TA. Phyllodes tumors of the breast: a review of 32 cases. Am Surg. 2000;66(4):360\u20136.","journal-title":"Am Surg"},{"issue":"10","key":"588_CR3","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1002\/1097-0142(19930515)71:10<3020::AID-CNCR2820711022>3.0.CO;2-G","volume":"71","author":"L Bernstein","year":"1993","unstructured":"Bernstein L, Deapen D, Ross RK. The descriptive epidemiology of malignant cystosarcoma phyllodes tumors of the breast. Cancer. 1993;71(10):3020\u20134.","journal-title":"Cancer"},{"issue":"4","key":"588_CR4","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1309\/U6DVBFM81MLJC1FN","volume":"123","author":"PH Tan","year":"2005","unstructured":"Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hilmy M, Hung H, Selvarajan S, Bay BH. Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol. 2005;123(4):529\u201340.","journal-title":"Am J Clin Pathol"},{"issue":"9","key":"588_CR5","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1001\/archsurg.138.9.987","volume":"138","author":"IK Komenaka","year":"2003","unstructured":"Komenaka IK, El-Tamer M, Pile-Spellman E, Hibshoosh H. Core needle biopsy as a diagnostic tool to differentiate phyllodes tumor from fibroadenoma. Arch Surg. 2003;138(9):987\u201390.","journal-title":"Arch Surg"},{"issue":"3","key":"588_CR6","doi-asserted-by":"publisher","first-page":"310","DOI":"10.6004\/jnccn.2018.0012","volume":"16","author":"WJ Gradishar","year":"2018","unstructured":"Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, et al. Breast Cancer, version 4.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2018;16(3):310\u201320.","journal-title":"J Natl Compr Cancer Netw"},{"issue":"12","key":"588_CR7","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1002\/1097-0142(19890615)63:12<2532::AID-CNCR2820631229>3.0.CO;2-Q","volume":"63","author":"B Salvadori","year":"1989","unstructured":"Salvadori B, Cusumano F, Del Bo R, Delledonne V, Grassi M, Rovini D, Saccozzi R, Andreola S, Clemente C. Surgical treatment of phyllodes tumors of the breast. Cancer. 1989;63(12):2532\u20136.","journal-title":"Cancer"},{"issue":"Suppl 2","key":"588_CR8","doi-asserted-by":"publisher","first-page":"S36","DOI":"10.1038\/modpathol.2010.34","volume":"23","author":"M Bilous","year":"2010","unstructured":"Bilous M. Breast core needle biopsy: issues and controversies. Mod Pathol. 2010;23(Suppl 2):S36\u201345.","journal-title":"Mod Pathol"},{"issue":"5","key":"588_CR9","doi-asserted-by":"crossref","first-page":"713","DOI":"10.5858\/133.5.713","volume":"133","author":"D Giri","year":"2009","unstructured":"Giri D. Recurrent challenges in the evaluation of fibroepithelial lesions. Arch Pathol Lab Med. 2009;133(5):713\u201321.","journal-title":"Arch Pathol Lab Med"},{"issue":"8","key":"588_CR10","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1177\/1066896914548763","volume":"22","author":"TJ Lawton","year":"2014","unstructured":"Lawton TJ, Acs G, Argani P, Farshid G, Gilcrease M, Goldstein N, Koerner F, Rowe JJ, Sanders M, Shah SS, et al. Interobserver variability by pathologists in the distinction between cellular fibroadenomas and phyllodes tumors. Int J Surg Pathol. 2014;22(8):695\u20138.","journal-title":"Int J Surg Pathol"},{"issue":"1","key":"588_CR11","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.humpath.2015.09.001","volume":"47","author":"S Bandyopadhyay","year":"2016","unstructured":"Bandyopadhyay S, Barak S, Hayek K, Thomas S, Saeed H, Beydoun R, Shi D, Arabi H, Ruterbusch J, Cote M, et al. Can problematic fibroepithelial lesions be accurately classified on core needle biopsies? Hum Pathol. 2016;47(1):38\u201344.","journal-title":"Hum Pathol"},{"issue":"1","key":"588_CR12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13058-016-0692-6","volume":"18","author":"WJ Tan","year":"2016","unstructured":"Tan WJ, Cima I, Choudhury Y, Wei X, Lim JC, Thike AA, Tan MH, Tan PH. A five-gene reverse transcription-PCR assay for pre-operative classification of breast fibroepithelial lesions. Breast Cancer Res. 2016;18(1):31.","journal-title":"Breast Cancer Res"},{"issue":"8","key":"588_CR13","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1038\/ng.3037","volume":"46","author":"WK Lim","year":"2014","unstructured":"Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, et al. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014;46(8):877\u201380.","journal-title":"Nat Genet"},{"issue":"9","key":"588_CR14","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1136\/jclinpath-2015-202896","volume":"68","author":"CC Ng","year":"2015","unstructured":"Ng CC, Tan J, Ong CK, Lim WK, Rajasegaran V, Nasir ND, Lim JC, Thike AA, Salahuddin SA, Iqbal J, et al. MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases. J Clin Pathol. 2015;68(9):685\u201391.","journal-title":"J Clin Pathol"},{"issue":"10","key":"588_CR15","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1038\/bjc.2015.116","volume":"112","author":"M Yoshida","year":"2015","unstructured":"Yoshida M, Sekine S, Ogawa R, Yoshida H, Maeshima A, Kanai Y, Kinoshita T, Ochiai A. Frequent MED12 mutations in phyllodes tumours of the breast. Br J Cancer. 2015;112(10):1703\u20138.","journal-title":"Br J Cancer"},{"issue":"11","key":"588_CR16","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/ng.3409","volume":"47","author":"J Tan","year":"2015","unstructured":"Tan J, Ong CK, Lim WK, Ng CC, Thike AA, Ng LM, Rajasegaran V, Myint SS, Nagarajan S, Thangaraju S, et al. Genomic landscapes of breast fibroepithelial tumors. Nat Genet. 2015;47(11):1341\u20135.","journal-title":"Nat Genet"},{"issue":"8","key":"588_CR17","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1038\/bjc.2015.326","volume":"113","author":"M Yoshida","year":"2015","unstructured":"Yoshida M, Ogawa R, Yoshida H, Maeshima A, Kanai Y, Kinoshita T, Hiraoka N, Sekine S. TERT promoter mutations are frequent and show association with MED12 mutations in phyllodes tumors of the breast. Br J Cancer. 2015;113(8):1244\u20138.","journal-title":"Br J Cancer"},{"issue":"4","key":"588_CR18","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1002\/path.4672","volume":"238","author":"S Piscuoglio","year":"2016","unstructured":"Piscuoglio S, Ng CK, Murray M, Burke KA, Edelweiss M, Geyer FC, Macedo GS, Inagaki A, Papanastasiou AD, Martelotto LG, et al. Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression. J Pathol. 2016;238(4):508\u201318.","journal-title":"J Pathol"},{"issue":"11","key":"588_CR19","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1016\/j.humpath.2013.06.009","volume":"44","author":"A Cimino-Mathews","year":"2013","unstructured":"Cimino-Mathews A, Hicks JL, Sharma R, Vang R, Illei PB, De Marzo A, Emens LA, Argani P. A subset of malignant phyllodes tumors harbors alterations in the Rb\/p16 pathway. Hum Pathol. 2013;44(11):2494\u2013500.","journal-title":"Hum Pathol"},{"issue":"2","key":"588_CR20","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1046\/j.1365-2559.1999.00682.x","volume":"35","author":"RM Feakins","year":"1999","unstructured":"Feakins RM, Mulcahy HE, Nickols CD, Wells CA. p53 expression in phyllodes tumours is associated with histological features of malignancy but does not predict outcome. Histopathology. 1999;35(2):162\u20139.","journal-title":"Histopathology"},{"issue":"3","key":"588_CR21","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/modpathol.3880282","volume":"14","author":"CG Kleer","year":"2001","unstructured":"Kleer CG, Giordano TJ, Braun T, Oberman HA. Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast. Mod Pathol. 2001;14(3):185\u201390.","journal-title":"Mod Pathol"},{"key":"588_CR22","unstructured":"FibroPhyllo\u2122 Tissue Test. Make the Right Cut. https:\/\/www.lucencedx.com\/category\/media-release\/ . 2018."},{"key":"588_CR23","doi-asserted-by":"crossref","unstructured":"Koh VCY, Ng CCY, Bay BH, Teh BT, Tan PH. The utility of a targeted gene mutation panel in refining the diagnosis of breast phyllodes tumours. Pathology. 2019.","DOI":"10.1016\/j.pathol.2019.04.005"},{"issue":"7","key":"588_CR24","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.pathol.2017.07.011","volume":"49","author":"J Yeong","year":"2017","unstructured":"Yeong J, Thike AA, Young Ng CC, Md Nasir ND, Loh K, Teh BT, Tan PH. A genetic mutation panel for differentiating malignant phyllodes tumour from metaplastic breast carcinoma. Pathology. 2017;49(7):786\u20139.","journal-title":"Pathology"},{"key":"588_CR25","unstructured":"Lakhani SR. WHO classification of Tumours of the breast. International Agency for Research on Cancer. 2012."},{"issue":"2","key":"588_CR26","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbs017","volume":"14","author":"H Thorvaldsd\u00f3ttir","year":"2013","unstructured":"Thorvaldsd\u00f3ttir H, Robinson JT, Mesirov JP. Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14(2):178\u201392.","journal-title":"Brief Bioinform"},{"issue":"8","key":"588_CR27","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1245\/s10434-017-5847-x","volume":"24","author":"C Ihemelandu","year":"2017","unstructured":"Ihemelandu C, Fernandez S, Sugarbaker PH. A prognostic model for predicting overall survival in patients with peritoneal surface malignancy of an Appendiceal origin treated with Cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy. Ann Surg Oncol. 2017;24(8):2266\u201372.","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"588_CR28","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s00428-011-1184-9","volume":"460","author":"N Ludyga","year":"2012","unstructured":"Ludyga N, Grunwald B, Azimzadeh O, Englert S, Hofler H, Tapio S, Aubele M. Nucleic acids from long-term preserved FFPE tissues are suitable for downstream analyses. Virchows Arch. 2012;460(2):131\u201340.","journal-title":"Virchows Arch"},{"issue":"4","key":"588_CR29","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1089\/bio.2014.0010","volume":"12","author":"V Adem\u00e0","year":"2014","unstructured":"Adem\u00e0 V, Torres E, Sol\u00e9 F, Serrano S, Bellosillo B. Paraffin treasures: do they last forever? Biopreserv Biobank. 2014;12(4):281\u20133.","journal-title":"Biopreserv Biobank"},{"issue":"4","key":"588_CR30","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00428-017-2213-0","volume":"471","author":"A Guyard","year":"2017","unstructured":"Guyard A, Boyez A, Pujals A, Robe C. Tran Van Nhieu J, Allory Y, Moroch J, Georges O, Fournet JC, Zafrani ES et al: DNA degrades during storage in formalin-fixed and paraffin-embedded tissue blocks. Virchows Arch. 2017;471(4):491\u2013500.","journal-title":"Virchows Arch"},{"issue":"1","key":"588_CR31","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1373\/clinchem.2014.223040","volume":"61","author":"H Do","year":"2015","unstructured":"Do H, Dobrovic A. Sequence artifacts in DNA from formalin-fixed tissues: causes and strategies for minimization. Clin Chem. 2015;61(1):64\u201371.","journal-title":"Clin Chem"},{"issue":"4","key":"588_CR32","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1158\/1541-7786.MCR-14-0578","volume":"13","author":"AK Cani","year":"2015","unstructured":"Cani AK, Hovelson DH, McDaniel AS, Sadis S, Haller MJ, Yadati V, Amin AM, Bratley J, Bandla S, Williams PD, et al. Next-gen sequencing exposes frequent MED12 mutations and actionable therapeutic targets in Phyllodes tumors. Mol Cancer Res. 2015;13(4):613\u20139.","journal-title":"Mol Cancer Res"},{"issue":"7","key":"588_CR33","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/cam4.462","volume":"4","author":"S Nagasawa","year":"2015","unstructured":"Nagasawa S, Maeda I, Fukuda T, Wu W, Hayami R, Kojima Y, Tsugawa K, Ohta T. MED12 exon 2 mutations in phyllodes tumors of the breast. Cancer Med. 2015;4(7):1117\u201321.","journal-title":"Cancer Med"},{"issue":"5","key":"588_CR34","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1111\/his.12712","volume":"67","author":"S Piscuoglio","year":"2015","unstructured":"Piscuoglio S, Murray M, Fusco N, Marchi\u00f2 C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, et al. MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast. Histopathology. 2015;67(5):719\u201329.","journal-title":"Histopathology"},{"issue":"51","key":"588_CR35","doi-asserted-by":"publisher","first-page":"84428","DOI":"10.18632\/oncotarget.12991","volume":"7","author":"M La\u00e9","year":"2016","unstructured":"La\u00e9 M, Gardrat S, Rondeau S, Richardot C, Caly M, Chemlali W, Vacher S, Couturier J, Mariani O, Terrier P, et al. MED12 mutations in breast phyllodes tumors: evidence of temporal tumoral heterogeneity and identification of associated critical signaling pathways. Oncotarget. 2016;7(51):84428\u201338.","journal-title":"Oncotarget"},{"issue":"3","key":"588_CR36","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1111\/his.12764","volume":"68","author":"HC Lien","year":"2016","unstructured":"Lien HC, Huang CS, Yang YW, Jeng YM. Mutational analysis of MED12 exon 2 in a spectrum of fibroepithelial tumours of the breast: implications for pathogenesis and histogenesis. Histopathology. 2016;68(3):433\u201341.","journal-title":"Histopathology"},{"key":"588_CR37","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41523-017-0042-6","volume":"3","author":"F Pareja","year":"2017","unstructured":"Pareja F, Geyer FC, Kumar R, Selenica P, Piscuoglio S, Ng CKY, Burke KA, Edelweiss M, Murray MP, Brogi E, et al. Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways. NPJ Breast Cancer. 2017;3:40.","journal-title":"NPJ Breast Cancer"},{"issue":"1","key":"588_CR38","first-page":"105","volume":"1805","author":"A Marusyk","year":"2010","unstructured":"Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805(1):105\u201317.","journal-title":"Biochim Biophys Acta"},{"key":"588_CR39","unstructured":"Key Demographic Trends. http:\/\/www.singstatgovsg\/publications\/publications_and_papers\/cop2010\/census_2010_advance_census_release\/key_demographic_trendspdf . 2010."}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-019-0588-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12920-019-0588-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-019-0588-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:14:12Z","timestamp":1695341652000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-019-0588-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,23]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["588"],"URL":"https:\/\/doi.org\/10.1186\/s12920-019-0588-2","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,23]]},"assertion":[{"value":"10 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted with the approval of the SingHealth Centralized Institutional Review Board (CIRB Ref: 2016\/2819). A waiver of consent was granted given the retrospective nature of the project, and that archival tissue was used.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"NA","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"142"}}