Multi-omics approach to infer cancer therapeutic targets on chromosome 20q across tumor types
Abstract - 2898 PDF - 704Abstract
The identification of good targets is a critical step for the development of targeted therapies for cancer treatment. Here, we used a multi-omics approach to delineate potential targets on chromosome 20q, which frequently shows a complex pattern of DNA copy number amplification in many human cancers suggesting the presence of multiple driver genes. By comparing the amounts of individual mRNAs in cancer from 11 different human tissues with those in their corresponding normal tissues, we identified 18 genes that were robustly elevated across human cancers. Moreover, we found that higher expression levels of a majority of these genes were associated with poor prognosis in many human cancer types. Using DNA copy number and expression data for all 18 genes obtained from The Cancer Genome Atlas project, we discovered that amplification is a major mechanism driving overexpression of these 18 genes in the majority of human cancers. Our integrated analysis suggests that 18 genes on chromosome 20q might serve as novel potential molecular targets for targeted cancer therapy.
Keywords
Full Text:
PDFReferences
Goldman JM, Melo JV. Chronic myeloid leukemia – Advances in biology and new approaches to treatment. N Engl J Med 2003; 349: 1451–1464. doi: 10.1056/NEJMra020777.
Fausel C. Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm 2007; 64(24): S9–S15. doi: 10.2146/ajhp070482.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, et al. Mutations of the BRAF gene in human cancer. Nature 2002l; 417: 949–954. doi: 10.1038/nature00766.
Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, et al. Combined vemurafenib and cobimetinib in BRAF- mutated melanoma. N Engl J Med 2014; 371: 1867–1876. doi: 10.1056/NEJMoa1408868.
Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor- Tarh D, et al. High HER2 expression correlates with response to the combination of lapatinib and trastuzumab. Clin Cancer Res 2015; 21: 569–576. doi: 10.1158/1078-0432.CCR-14-1824.
Snijders AM, Fridlyand J, Mans DA, Segraves R, Jain AN, et al. Shaping of tumor and drug-resistant genomes by instability and selection. Oncogene 2003; 22: 4370–4379. doi: 10.1038/sj.onc.1206482.
Wilting SM, Snijders PJF, Meijer GA, Ylstra B, van den Ijssel PRLA, et al. Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix. J Pathol 2006; 209(2): 220–230. doi: 10.1002/path.1966.
Fridlyand J, Snijders AM, Ylstra B, Li H, Olshen A, et al. Breast tumor copy number aberration phenotypes and genomic instability. BMC Cancer 2006; 6: 96. doi: 10.1186/1471-2407-6-96.
Aguirre-Gamboa R, Gomez-Rueda H, Martínez-Ledesma E, Martínez-Torteya A, Chacolla-Huaringa R, et al. SurvExpress: An online biomarker validation tool and database for cancer gene expression data using survival analysis. PLoS ONE 2013; 8: e74250. doi: 10.1371/journal.pone.0074250. 10. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013; 6(269): pl1. doi: 10.1126/scisignal.2004088.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, et al. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012; 2: 401–404. doi: 10.1158/2159-8290.CD-12-0095.
Wang J, Duncan D, Shi Z, Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): Update 2013. Nucleic Acids Res 2013; 41(W1): W77–W83. doi: 10.1093/nar/gkt439.
Katayama H, Brinkley WR, Sen S. The Aurora kinases: Role in cell transformation and tumorigenesis. Cancer Metastasis Rev 2003; 22(4): 451–464. doi: 10.1023/A:1023789416385.
Warner SL, Bearss DJ, Han H, Von Hoff DD. Targeting Aurora-2 kinase in cancer. Mol Cancer Ther 2003; 2(6): 589–595.
Kufer TA, Silljé HH, Körner R, Gruss OJ, Meraldi P, et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 2002; 158(4): 617–623. doi: 10.1083/jcb.200204155.
Malumbres M, Pérez de Castro I. Aurora kinase A inhibitors: Promising agents in antitumoral therapy. Expert Opin Ther Targets 2014; 18(12): 1377–1393. doi: 10.1517/14728222.2014.956085.
Katayama H, Sen S. Aurora kinase inhibitors as anticancer molecules. Biochim Biophys Acta 2010; 1799(10–12): 829–839. doi: 10.1016/j.bbagrm.2010.09.004.
Blower MD, Nachury M, Heald R, Weis K. A Rae1- containing ribonucleoprotein complex is required for mitotic spindle assembly. Cell 2005; 121(2): 223–234. doi: 10.1016/j.cell.2005.02.016.
Babu JR, Jeganathan KB, Baker DJ, Wu X, Kang-Decker N, et al. Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. J Cell Biol 2003; 160(3): 341–353. doi: 10.1083/jcb.200211048.
Cheng J, Gao J, Shuai X, Tao K. Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: A meta-analysis of individual studies. Oncotarget 2016; 7(17): 24314–24325. doi: 10.18632/oncotarget.8237.
Cohen PA, Donini CF, Nguyen NT, Lincet H, Vendrell JA. The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker value. Oncotarget 2015; 6(39): 41566–41581. doi: 10.18632/oncotarget.5893.
Chen YY, Li ZZ, Ye YY, Xu F, Niu RJ, et al. Knockdown of SALL4 inhibits the proliferation and reverses the resistance of MCF-7/ADR cells to doxorubicin hydrochloride. BMC Mol Biol 2016; 17: 6. doi: 10.1186/s12867-016-0055-y.
Littlepage LE, Adler AS, Kouros-Mehr H, Huang G, Chou J, et al. The transcription factor ZNF217 is a prognostic biomarker and therapeutic target during breast cancer progression. Cancer Discov 2012; 2: 638–651. doi: 10.1158/2159-8290.CD-12-0093.
Rosen SD, Lemjabbar-Alaoui H. Sulf-2: An extracellular modulator of cell signaling and a cancer target candidate. Expert Opin Ther Targets 2010; 14(9): 935–949. doi: 10.1517/14728222.2010.504718.
Lui NS, Yang YW, van Zante A, Buchanan P, Jablons DM, et al. SULF2 expression is a potential diagnostic and prognostic marker in lung cancer. PLoS ONE 2016; 11: e0148911. doi: 10.1371/journal.pone.0148911.
Yuksel UM, Turker I, Dilek G, Dogan L, Gulcelik MA, et al. Does CSE1L overexpression affect distant metastasis development in breast cancer? Oncol Res Treat 2015; 38(9): 431–434. doi: 10.1159/000438501.
Tai CJ, Shen SC, Lee WR, Liao CF, Deng WP, et al. Increased cellular apoptosis susceptibility (CSE1L/CAS) protein expression promotes protrusion extension and enhances migration of MCF-7 breast cancer cells. Exp Cell Res 2010; 316(17): 2969–2981. doi: 10.1016/j.yexcr.2010.07.019.
Walian PJ, Hang B, Mao JH. Prognostic significance of FAM83D gene expression across human cancer types. Oncotarget 2016; 7(3): 3332–3340. doi: 10.18632/oncotarget.6620.
Varisli L. Meta-analysis of the expression of the mitosis-related gene FAM83D. Oncol Lett 2012; 4(6): 1335–1340. doi: 10.3892/ol.2012.925.
Liao W, Liu W, Liu X, Yuan Q, Ou Y, et al. Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma. Oncotarget 2015; 6(27): 24132– 24147. doi: 10.18632/oncotarget.4432.
Wang D, Han S, Peng R, Wang X, Yang XX, et al. FAM83D activates the MEK/ERK signaling pathway and promotes cell proliferation in hepatocellular carcinoma. Biochem Biophys Res Commun 2015; 458(2): 313–320. doi: 10.1016/j.bbrc.2015.01.108.
Wang Z, Liu Y, Zhang P, Zhang W, Wang W, et al. FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7. Oncotarget 2013; 4(12): 2476–2486. doi: 10.18632/oncotarget.1581.
DOI: http://dx.doi.org/10.18282/amor.v2.i4.141
Refbacks
- There are currently no refbacks.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Comments on this article
by Fábio Pedrosa (2018-02-15)
by Nádia Salas (2018-03-04)
by LunaResende Muniz (2018-06-16)
by KamillyGil Amorim (2018-06-21)
by AmandaGouveia Barreto (2018-06-23)
by AnaClaraAlves Maciel (2018-06-28)
by MariaJuliaSalgueiro Albuquerque (2018-06-28)
by luciana lima (2018-06-29)
by MarcelaXimenes Ferrari (2018-07-08)
by Alfonzo Cadell (2018-07-11)
by Pilar Allison (2018-07-11)
by MarianeBeira-Mar Santana (2018-07-13)
by Nate Ferguson (2018-07-16)
by Davi Lucca Martins (2018-07-19)
by Maria Mariana Moraes (2018-07-19)
by Davi Lucca Martins (2018-07-22)
by Vicente Aragão (2018-07-22)
by Vicente Aragão (2018-07-27)
by Davi Lucca Martins (2018-07-27)
by Vicente Aragão (2018-07-28)
by Beatriz Gonçalves (2018-07-29)
by Davi Lucca Martins (2018-07-29)
by Mucio Rosa (2018-07-31)
by Miah Vega (2018-08-01)
by issia cristian (2018-08-03)
by Anesio Dominato (2018-08-07)
by Ona Weeks (2018-08-12)
by Wilbur Plath (2018-08-12)
by Charmain Marrone (2018-08-12)
by Davi Lucca Martins (2018-08-14)
by Inge Mennell (2018-08-14)
by Stanley Mault (2018-08-16)
by Alfonzo Bingle (2018-08-17)
by Aundrea Metters (2018-08-17)
by Glinda Motter (2018-08-17)
by Lamar Laster (2018-08-17)
by Bianca Brinkman (2018-08-17)
by Lupe Chubb (2018-08-17)
by Milagros Hardwicke (2018-08-17)
by Jewell Gregg (2018-08-17)
by Lina Hudak (2018-08-17)
by Fallon Kelsey (2018-08-17)
by Dwight Keller (2018-08-17)
by Lashawn Hillyard (2018-08-17)
by Barbara Macaulay (2018-08-17)
by Orville Harold (2018-08-17)
by Dante Kirk (2018-08-17)
by Ramon Arroyo (2018-08-17)
by Lynn Beardsmore (2018-08-17)
by Lonna Cavazos (2018-08-17)
by Danuta Holton (2018-08-17)
by Kelle Tompkins (2018-08-17)
by Kevin Shedden (2018-08-17)
by Soila Theus (2018-08-17)
by Isabel Nielsen (2018-08-17)
by Dyan Franks (2018-08-17)
by Leola Madden (2018-08-17)
by Ivy Birrell (2018-08-17)
by Hung Liston (2018-08-17)
by Ariel Maddock (2018-08-17)
by Rosita McBryde (2018-08-17)
by Williams Stella (2018-08-17)
by Harriet Sambell (2018-08-17)
by Virgil Santoro (2018-08-17)
by Carma Roddy (2018-08-17)
by Emory Fortier (2018-08-17)
by Marilyn Weldon (2018-08-17)
by Arnulfo Sennitt (2018-08-17)
by Gloria Weaver (2018-08-17)
by Trent Woolacott (2018-08-17)
by Fred Barber (2018-08-17)
by Shannan Musquito (2018-08-17)
by Leandro Riley (2018-08-17)
by Mavis Dossett (2018-08-17)
by Bert Marko (2018-08-18)
by Rosalyn Kail (2018-08-18)
by Elton Doty (2018-08-18)
by Mei Benning (2018-08-18)
by Victoria Macintosh (2018-08-18)
by Jeremy Martinovich (2018-08-18)
by Bart Norfleet (2018-08-18)
by Delores Wymark (2018-08-18)
by Brodie Gilliland (2018-08-18)
by Shelia Boose (2018-08-18)
by Keesha Paton (2018-08-18)
by Jon Macfarlan (2018-08-18)
by Darnell Gorman (2018-08-18)
by Marylin Colunga (2018-08-18)
by Deana Deloach (2018-08-18)
by Vida Cooch (2018-08-18)
by Soila Theus (2018-08-18)
by Soila Theus (2018-08-18)
by Penney Stage (2018-08-18)
by Adell Stace (2018-08-18)
by Jessika Jensen (2018-08-18)
by Sima Fletcher (2018-08-18)
by Chloe Sinclaire (2018-08-18)
by Luann Bunbury (2018-08-18)
by Ivy Birrell (2018-08-18)
by Evie Beeler (2018-08-18)
by Tracy Parkes (2018-08-18)
by Lora Ibarra (2018-08-18)
by Fallon Whitcomb (2018-08-18)
by Wyatt Maldonado (2018-08-18)
by Kristie Braden (2018-08-18)
by Zane Danielson (2018-08-18)
by Barbara Cockett (2018-08-18)
by Sue Troedel (2018-08-18)
by Loretta Dullo (2018-08-18)
by Oscar Hartford (2018-08-18)
by Janine Thibault (2018-08-18)
by Stefanie Solander (2018-08-18)
by Kelle Tompkins (2018-08-18)
by Roscoe Dunaway (2018-08-18)
by Celia Jamieson (2018-08-18)
by Kevin Shedden (2018-08-18)
by Kevin Shedden (2018-08-18)
by Madge Curlewis (2018-08-18)
by Kevin Shedden (2018-08-18)
by Concetta Vandermark (2018-08-18)
by Genia Driver (2018-08-18)
by Isabel Nielsen (2018-08-18)
by Carole Ashmore (2018-08-18)
by Bernice Carner (2018-08-18)
by Ariel Maddock (2018-08-18)
by Jonas Peters (2018-08-18)
by Dyan Franks (2018-08-18)
by Darwin Florey (2018-08-18)
by Denese Venning (2018-08-18)
by Sam Harding (2018-08-18)
by Harriett Hervey (2018-08-18)
by Tosha Wheare (2018-08-18)
by Giuseppe Solomon (2018-08-18)
by Porter Poland (2018-08-18)
by Harriet Sambell (2018-08-18)
by Elizabet Carrell (2018-08-18)
by Marianne Ross (2018-08-18)
by Virgil Santoro (2018-08-18)
by Rosita McBryde (2018-08-18)
by Harriet Sambell (2018-08-18)
by Rosita McBryde (2018-08-18)
by Virgil Santoro (2018-08-18)
by Sonja Levay (2018-08-18)
by Gloria Weaver (2018-08-18)
by Linnea Lowery (2018-08-18)
by Larue Connal (2018-08-18)
by Hung Liston (2018-08-18)
by Carma Roddy (2018-08-18)
by Bert Marko (2018-08-18)
by Lula Furman (2018-08-18)
by Henrietta Gunderson (2018-08-18)
by Kevin Shedden (2018-08-18)
by Jeremy Martinovich (2018-08-18)
by Dyan Franks (2018-08-18)
by Keesha Paton (2018-08-18)
by Patrice Petersen (2018-08-19)
by Louis Knutson (2018-08-19)
by Lance Siede (2018-08-19)
by Renee Wong (2018-08-19)
by Zandra Elmslie (2018-08-20)
by Ava Spyer (2018-08-20)
by Matt Kish (2018-08-20)
by Chong Brannon (2018-08-20)
by Autumn Odriscoll (2018-08-21)
by Twila Mulvany (2018-08-21)
by Patricia Tomczak (2018-08-21)
by Lorenza Loveless (2018-08-21)
by Jay Jacquez (2018-08-21)
by Zandra Elmslie (2018-08-21)
by Rebekah Fuhrmann (2018-08-21)
by Zandra Elmslie (2018-08-21)
by Matt Kish (2018-08-21)
by Rosalina Bowmaker (2018-08-21)
by Zandra Elmslie (2018-08-21)
by Fawn Bechtel (2018-08-21)
by Dewitt Hulsey (2018-08-21)
by Maple MacCarthy (2018-08-21)
by Maddison McPhillamy (2018-08-21)
by Zandra Elmslie (2018-08-22)
by Cary Villegas (2018-08-22)
by Caryn Hoffnung (2018-08-22)
by Merissa Spivey (2018-08-22)
by Jacinto King (2018-08-22)
by Cheryle Sifford (2018-08-22)
by Jonelle Lamb (2018-08-22)
by Aubrey Keen (2018-08-22)
by Elana Ash (2018-08-22)
by Matt Mccool (2018-08-22)
by Clara Gomez (2018-08-22)
by Gale Frasier (2018-08-22)
by Roxanna Giltner (2018-08-22)
by Teodoro Stockman (2018-08-22)
by Cary Villegas (2018-08-22)
by Rolando Wells (2018-08-23)
by Roma Dooley (2018-08-23)
by Josette Sinclair (2018-08-23)
by Alfonzo Maur (2018-08-23)
by Tosha McIntyre (2018-08-24)
by Roseanne Hebert (2018-08-24)
by Octavia Bigge (2018-08-30)
by Buck Higgins (2018-08-30)
by Randy Boucaut (2018-08-30)
by Athena Laby (2018-08-31)
by Jaime Epp (2018-08-31)
by Ulrike Flack (2018-08-31)
by Buck Higgins (2018-08-31)
by Mariano Mayorga (2018-08-31)
by Adrianna Blackman (2018-08-31)
by Murray Knetes (2018-08-31)
by Calvin St Julian (2018-08-31)
by Benjamin McGeorge (2018-08-31)
by Brett Minns (2018-08-31)
by Octavia Minner (2018-08-31)
by Giselle De Chair (2018-08-31)
by Luigi Heaton (2018-08-31)
by Misty Rivers (2018-08-31)
by Theda Creighton (2018-08-31)
by Bradly Deloach (2018-08-31)
by Dewitt Lipscombe (2018-08-31)
by Kristal Massie (2018-08-31)
by Alannah McRoberts (2018-08-31)
by Terence Crosby (2018-08-31)
by Sarah Jordan (2018-08-31)
by Columbus Brumby (2018-08-31)
by Carmela Skene (2018-08-31)
by Buck Higgins (2018-08-31)
by Benjamin McGeorge (2018-08-31)
by Athena Laby (2018-08-31)
by Athena Laby (2018-09-01)
by Benjamin McGeorge (2018-09-01)
by Bradly Deloach (2018-09-03)
by Benjamin McGeorge (2018-09-04)
by Luigi Heaton (2018-09-05)
by Benjamin McGeorge (2018-09-05)
by Theda Creighton (2018-09-05)
by Benjamin McGeorge (2018-09-05)
by Benjamin McGeorge (2018-09-05)
by Benjamin McGeorge (2018-09-06)
by Athena Laby (2018-09-06)
by Buck Higgins (2018-09-06)
by Benjamin McGeorge (2018-09-06)
by Benjamin McGeorge (2018-09-06)
by Benjamin McGeorge (2018-09-06)
by Theda Creighton (2018-09-06)
by Celsa Simone (2018-09-06)
by Benjamin McGeorge (2018-09-06)
by Luigi Heaton (2018-09-06)
by Ona Beatty (2018-09-06)
by Louise Lange (2018-09-06)
by Buck Higgins (2018-09-06)
by Luigi Heaton (2018-09-06)
by Buck Higgins (2018-09-06)
by Ryder Perkinson (2018-09-06)
by Buck Higgins (2018-09-06)
by Jonathon Dickerman (2018-09-06)
by Murray Kaur (2018-09-06)
by Celsa Simone (2018-09-07)
by Celsa Simone (2018-09-07)
by Theda Creighton (2018-09-07)
by Athena Laby (2018-09-07)
by Buck Higgins (2018-09-07)
by Benjamin McGeorge (2018-09-07)
by Luigi Heaton (2018-09-07)
by Bradly Deloach (2018-09-07)
by Alannah McRoberts (2018-09-07)
by Luigi Heaton (2018-09-07)
by Sarah Jordan (2018-09-07)
by Luigi Heaton (2018-09-07)
by Luigi Heaton (2018-09-07)
by Luigi Heaton (2018-09-08)
by Buck Higgins (2018-09-08)
by Benjamin McGeorge (2018-09-08)
by Athena Laby (2018-09-08)
by Buck Higgins (2018-09-08)
by Buck Higgins (2018-09-08)
by Celsa Simone (2018-09-08)
by Bradly Deloach (2018-09-08)
by Celsa Simone (2018-09-08)
by Ona Beatty (2018-09-08)
by Luigi Heaton (2018-09-08)
by Jonathon Dickerman (2018-09-08)
by Jonathon Dickerman (2018-09-08)
by Jonathon Dickerman (2018-09-08)
by Theda Creighton (2018-09-08)
by Buck Higgins (2018-09-08)
by Athena Laby (2018-09-08)
by Athena Laby (2018-09-09)
by Jonathon Dickerman (2018-09-09)
by Murray Kaur (2018-09-09)
by Sarah Jordan (2018-09-09)
by Benjamin McGeorge (2018-09-09)
by Louise Lange (2018-09-09)
by Luigi Heaton (2018-09-09)
by Alannah McRoberts (2018-09-09)
by Louise Lange (2018-09-09)
by Benjamin McGeorge (2018-09-09)
by Wagner Barros (2018-09-09)
by Bradly Deloach (2018-09-09)
by Alannah McRoberts (2018-09-09)
by Theda Creighton (2018-09-09)
by Theda Creighton (2018-09-09)
by Buck Higgins (2018-09-09)
by Theda Creighton (2018-09-09)
by Louise Lange (2018-09-09)
by Celsa Simone (2018-09-09)
by Benjamin McGeorge (2018-09-10)
by Athena Laby (2018-09-10)
by Bradly Deloach (2018-09-10)
by Buck Higgins (2018-09-10)
by Bradly Deloach (2018-09-10)
by Athena Laby (2018-09-10)
by Celsa Simone (2018-09-10)
by Murray Kaur (2018-09-10)
by Jonathon Dickerman (2018-09-10)
by Ona Beatty (2018-09-10)
by Ona Beatty (2018-09-10)
by Ona Beatty (2018-09-10)
by Louise Lange (2018-09-10)
by Louise Lange (2018-09-11)
by Athena Laby (2018-09-11)
by Jonathon Dickerman (2018-09-11)
by Ona Beatty (2018-09-11)
by Murray Kaur (2018-09-11)
by Buck Higgins (2018-09-11)
by Athena Laby (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Bradly Deloach (2018-09-12)
by Athena Laby (2018-09-12)
by Murray Kaur (2018-09-12)
by Bradly Deloach (2018-09-12)
by Buck Higgins (2018-09-12)
by Athena Laby (2018-09-12)
by Buck Higgins (2018-09-12)
by Buck Higgins (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Buck Higgins (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Luigi Heaton (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Bradly Deloach (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-12)
by Benjamin McGeorge (2018-09-13)
by Luigi Heaton (2018-09-13)
by Bradly Deloach (2018-09-13)
by Athena Laby (2018-09-13)
by Athena Laby (2018-09-13)
by Theda Creighton (2018-09-13)
by Bradly Deloach (2018-09-13)
by Alannah McRoberts (2018-09-13)
by Buck Higgins (2018-09-13)
by Murilo Ribeiro (2018-09-13)
by Buck Higgins (2018-09-14)
by Bradly Deloach (2018-09-14)
by Bradly Deloach (2018-09-14)
by Buck Higgins (2018-09-14)
by Sarah Jordan (2018-09-14)
by Athena Laby (2018-09-14)
by Murray Kaur (2018-09-14)
by Buck Higgins (2018-09-14)
by Athena Laby (2018-09-14)
by Jill Dowler (2018-09-14)
by Buck Higgins (2018-09-14)
by Buck Higgins (2018-09-14)
by Jaxon Heckman (2018-09-15)
by Athena Laby (2018-09-15)
by Bradly Deloach (2018-09-15)
by Benjamin McGeorge (2018-09-15)
by Sarah Jordan (2018-09-15)
by Benjamin McGeorge (2018-09-15)
by Buck Higgins (2018-09-15)
by Helena Barros (2018-09-15)
by Benjamin McGeorge (2018-09-15)
by Buck Higgins (2018-09-15)
by Bradly Deloach (2018-09-15)
by Athena Laby (2018-09-15)
by Athena Laby (2018-09-15)
by Benjamin McGeorge (2018-09-15)
by Athena Laby (2018-09-15)
by Athena Laby (2018-09-15)
by Buck Higgins (2018-09-15)
by Athena Laby (2018-09-16)
by Benjamin McGeorge (2018-09-16)
by Bradly Deloach (2018-09-16)
by Alannah McRoberts (2018-09-16)
by Theda Creighton (2018-09-16)
by Theda Creighton (2018-09-16)
by Luigi Heaton (2018-09-16)
by Sarah Jordan (2018-09-16)
by Theda Creighton (2018-09-16)
by Theda Creighton (2018-09-16)
by Buck Higgins (2018-09-16)
by Buck Higgins (2018-09-16)
by Luther Sons (2018-09-17)
by Luigi Spillman (2018-09-17)
by Pedro Thomas da Paz (2018-09-17)
by Liza Vanish (2018-09-18)
by Josette De Mole (2018-09-18)
by Katja Ibbott (2018-09-18)
by George Lavallee (2018-09-19)
by Armando Talbott (2018-09-19)
by Brigida Mallory (2018-09-19)
by Eli Moreira (2018-09-19)
by Aquilino Reis (2018-09-19)
by Damaris Deegan (2018-09-19)
by Jarrod McMahan (2018-09-19)
by Juliet Portus (2018-09-20)
by Kiera Wickens (2018-09-20)
by Marley Rocha (2018-09-20)
by Troy Fouch (2018-09-20)
by Evaldo Pacheco (2018-09-20)
by Alton Abe (2018-09-20)
by Dave Lefkowitz (2018-09-21)
by Dustin Childers (2018-09-21)
by Autumn Betche (2018-09-22)
by Elwood Jessup (2018-09-22)
by Samual Mattocks (2018-09-22)
by Natalia Lempriere (2018-09-22)
by Sarah Hincks (2018-09-22)
by Bradly Deloach (2018-09-22)
by Sylvester Ronan (2018-09-22)
by Clifford Feetham (2018-09-22)
by Alton Claude (2018-09-22)
by Yvette Ievers (2018-09-22)
by Buck Higgins (2018-09-22)
by Athena Laby (2018-09-22)
by Athena Laby (2018-09-22)
by Bradly Deloach (2018-09-22)
by Benjamin McGeorge (2018-09-22)
by Tracy Dawes (2018-09-23)
by Buck Higgins (2018-09-23)
by Bradly Deloach (2018-09-23)
by Lavina Estrada (2018-09-23)
by Tina Mccarter (2018-09-23)
by Athena Laby (2018-09-23)
by Benjamin McGeorge (2018-09-23)
by Athena Laby (2018-09-23)
by Bradly Deloach (2018-09-23)
by Cathy Eskridge (2018-09-23)
by Benjamin McGeorge (2018-09-23)
by Theda Creighton (2018-09-23)
by Theda Creighton (2018-09-23)
by Luigi Heaton (2018-09-23)
by Alina Cromwell (2018-09-24)
by Carroll Barnhart (2018-09-24)
by Lena Hardy (2018-09-24)
by Katlyn Lincoln (2018-09-24)
by Marcia Ketner (2018-09-24)
by Micheal Smartt (2018-09-24)
by Eula Flack (2018-09-24)
by Eula Flack (2018-09-24)
by Bradly Deloach (2018-09-24)
by Luigi Heaton (2018-09-24)
by Beth Primeaux (2018-09-24)
by Athena Laby (2018-09-24)
by Benjamin McGeorge (2018-09-24)
by Benjamin McGeorge (2018-09-24)
by Lee Daulton (2018-09-24)
by Athena Laby (2018-09-24)
by Luigi Heaton (2018-09-24)
by Tammy Dore (2018-09-24)
by Cody Jarrett (2018-09-25)
by Oliva Ogilvy (2018-09-25)
by Emil Stark (2018-09-25)
by Syreeta Virgo (2018-09-25)
by Luigi Heaton (2018-09-25)
by Isobel Child (2018-09-25)
by Amarilio Rangel (2018-09-25)
by Fausto Vinci (2018-09-25)
by Benjamin McGeorge (2018-09-25)
by Rick Reeves (2018-09-25)
by Athena Laby (2018-09-25)
by Bradly Deloach (2018-09-25)
by Athena Laby (2018-09-25)
by Theda Creighton (2018-09-25)
by Benjamin McGeorge (2018-09-25)
by Luigi Heaton (2018-09-25)
by Benjamin McGeorge (2018-09-25)
by Luigi Heaton (2018-09-25)
by Alcino Serna (2018-09-26)
by Bridgette Sabo (2018-09-26)
by Sherrie Goldstein (2018-09-26)
by Dotty Whitten (2018-09-26)
by Athena Laby (2018-09-26)
by Sarah Jordan (2018-09-27)
by Athena Laby (2018-09-27)
by Benjamin McGeorge (2018-09-27)
by Benjamin McGeorge (2018-09-27)
by Luigi Heaton (2018-09-27)
by Sylvester Claflin (2018-09-27)
by Luigi Heaton (2018-09-27)
by Theda Creighton (2018-09-27)
by Alannah McRoberts (2018-09-27)
by Percy Leflore (2018-09-28)
by Benjamin McGeorge (2018-09-28)
by Benjamin McGeorge (2018-09-28)
by Sanford Cheeseman (2018-09-28)
by Gabriela Chalmers (2018-09-28)
by Gabriela Chalmers (2018-09-29)
by Gabriela Chalmers (2018-09-29)
by Ada Cantamessa (2018-09-29)
by Candida Ewers (2018-09-29)
by Therese Piscitelli (2018-09-30)
by Bradly Deloach (2018-10-01)
by Alannah McRoberts (2018-10-01)
by Benjamin McGeorge (2018-10-01)
by Theda Creighton (2018-10-01)
by Bradly Deloach (2018-10-01)
by Athena Laby (2018-10-01)
by Athena Laby (2018-10-01)
by Theda Creighton (2018-10-02)
by Theda Creighton (2018-10-02)
by Theda Creighton (2018-10-02)
by Theda Creighton (2018-10-02)
by Mireya Lindrum (2018-10-02)
by Christie Santana (2018-10-02)
by Taylor Gaertner (2018-10-02)
by Theda Creighton (2018-10-02)
by Benjamin McGeorge (2018-10-02)
by Alannah McRoberts (2018-10-02)
by Kimberly Beirne (2018-10-02)
by Kimberly Beirne (2018-10-02)
by Uta Swain (2018-10-02)
by Alannah McRoberts (2018-10-02)
by Bradly Deloach (2018-10-02)
by Alannah McRoberts (2018-10-02)
by Collin Bruton (2018-10-03)
by Kathryn Brogan (2018-10-03)
by Donette Clopton (2018-10-04)
by Flora Roseby (2018-10-06)
by Donette Clopton (2018-10-06)
by Nola Strong (2018-10-06)
by Kristan Hughes (2018-10-06)
by Alfred Sisco (2018-10-06)
by Ruby O'Keeffe (2018-10-07)
by Flora Roseby (2018-10-07)
by Donette Clopton (2018-10-07)
by Nola Strong (2018-10-07)
by Nola Strong (2018-10-07)
by Nola Strong (2018-10-07)
by Regina Salisbury (2018-10-07)
by Connor Scerri (2018-10-07)
by Nola Strong (2018-10-07)
by Ezra Delapena (2018-10-08)
by Sonia Barbosa (2018-10-08)
by Donette Clopton (2018-10-08)
by Flora Roseby (2018-10-08)
by Flora Roseby (2018-10-08)
by Lashay Bracker (2018-10-08)
by Alfred Sisco (2018-10-08)
by Isidro Moorman (2018-10-08)
by Etsuko Abt (2018-10-08)
by Mike Lillard (2018-10-08)
by Tesha Dykes (2018-10-08)
by Leta Clow (2018-10-09)
by Dominik Supple (2018-10-09)
by Shonda Judd (2018-10-09)
by Nola Strong (2018-10-09)
by Nola Strong (2018-10-09)
by Lashay Bracker (2018-10-09)
by Donette Clopton (2018-10-09)
by Donette Clopton (2018-10-09)
by Junior Levesque (2018-10-09)
by Lashay Bracker (2018-10-09)
by Nola Strong (2018-10-09)
by Lashay Bracker (2018-10-09)
by Dinah Gleadow (2018-10-09)
by Javier Roderic (2018-10-09)
by Donette Clopton (2018-10-09)
by Shonda Judd (2018-10-09)
by Flora Roseby (2018-10-09)
by Lashay Bracker (2018-10-09)
by Flora Roseby (2018-10-09)
by Isidro Moorman (2018-10-09)
by Shonda Judd (2018-10-09)
by Lashonda Humphrey (2018-10-09)
by Isiah Judy (2018-10-09)
by Donette Clopton (2018-10-09)
by Lashay Bracker (2018-10-09)
by Flora Roseby (2018-10-09)
by Lashay Bracker (2018-10-09)
by Eddy Durkin (2018-10-09)
by Isidro Moorman (2018-10-09)
by Donette Clopton (2018-10-09)
by Cathern Camara (2018-10-09)
by Manuela Lockington (2018-10-09)
by Mike Lillard (2018-10-09)
by Mike Lillard (2018-10-09)
by Inge Donoghue (2018-10-09)
by Dominik Supple (2018-10-09)
by Dominik Supple (2018-10-09)
by Etsuko Abt (2018-10-10)
by Isidro Moorman (2018-10-10)
by Dominik Supple (2018-10-10)
by Isidro Moorman (2018-10-10)
by Donette Clopton (2018-10-10)
by Dominik Supple (2018-10-10)
by Loyd Aguayo (2018-10-10)
by Dominik Supple (2018-10-10)
by Donette Clopton (2018-10-10)
by Donette Clopton (2018-10-10)
by Nola Strong (2018-10-10)
by Etsuko Abt (2018-10-10)
by Leta Clow (2018-10-10)
by Donette Clopton (2018-10-10)
by Donette Clopton (2018-10-10)
by Etsuko Abt (2018-10-10)
by Tesha Dykes (2018-10-10)
by Leta Clow (2018-10-10)
by Shonda Judd (2018-10-10)
by Donette Clopton (2018-10-10)
by Donette Clopton (2018-10-10)
by Isabel Jess (2018-10-10)
by Etsuko Abt (2018-10-10)
by Etsuko Abt (2018-10-10)
by Donette Clopton (2018-10-10)
by Alfred Sisco (2018-10-10)
by Etsuko Abt (2018-10-10)
by Tesha Dykes (2018-10-10)
by Donette Clopton (2018-10-10)
by Lashay Bracker (2018-10-10)
by Etsuko Abt (2018-10-10)
by Etsuko Abt (2018-10-10)
by Tesha Dykes (2018-10-10)
by Donette Clopton (2018-10-10)
by Donette Clopton (2018-10-10)
by Etsuko Abt (2018-10-10)
by Nola Strong (2018-10-10)
by Donette Clopton (2018-10-10)
by Clarice Hoffnung (2018-10-10)
by Lashay Bracker (2018-10-10)
by Lashay Bracker (2018-10-10)
by Christy Seeley (2018-10-10)
by Lashay Bracker (2018-10-11)
by Donette Clopton (2018-10-11)
by Isidro Moorman (2018-10-11)
by Etsuko Abt (2018-10-11)
by Isidro Moorman (2018-10-11)
by Isidro Moorman (2018-10-11)
by Tesha Dykes (2018-10-11)
by Alfred Sisco (2018-10-11)
by Nola Strong (2018-10-11)
by Etsuko Abt (2018-10-11)
by Lashay Bracker (2018-10-11)
by Isidro Moorman (2018-10-11)
by Tesha Dykes (2018-10-11)
by Tesha Dykes (2018-10-11)
by Alfred Sisco (2018-10-11)
by Leta Clow (2018-10-11)
by Wanda Escobar (2018-10-11)
by Mike Lillard (2018-10-11)
by Dominik Supple (2018-10-11)
by Tesha Dykes (2018-10-11)
by Tesha Dykes (2018-10-11)
by Tesha Dykes (2018-10-11)
by Isidro Moorman (2018-10-11)
by Tesha Dykes (2018-10-11)
by Tesha Dykes (2018-10-11)
by Isidro Moorman (2018-10-11)
by Tesha Dykes (2018-10-11)
by Lashay Bracker (2018-10-12)
by Alfred Sisco (2018-10-12)
by Tesha Dykes (2018-10-12)
by Lashay Bracker (2018-10-12)
by Tesha Dykes (2018-10-12)
by Shonda Judd (2018-10-12)
by Tesha Dykes (2018-10-12)
by Leta Clow (2018-10-12)
by Leta Clow (2018-10-12)
by Alfred Sisco (2018-10-12)
by Lashay Bracker (2018-10-12)
by Mike Lillard (2018-10-12)
by Leta Clow (2018-10-12)
by Isidro Moorman (2018-10-12)
by Alfred Sisco (2018-10-12)
by Isidro Moorman (2018-10-12)
by Etsuko Abt (2018-10-12)
by Etsuko Abt (2018-10-12)
by Etsuko Abt (2018-10-12)
by Shonda Judd (2018-10-12)
by Lashay Bracker (2018-10-12)
by Shonda Judd (2018-10-13)
by Lashay Bracker (2018-10-13)
by Shonda Judd (2018-10-13)
by Lashay Bracker (2018-10-13)
by Christy Seeley (2018-10-13)
by Christy Seeley (2018-10-13)
by Lashay Bracker (2018-10-13)
by Christy Seeley (2018-10-13)
by Christy Seeley (2018-10-13)
by Christy Seeley (2018-10-13)
by Lashay Bracker (2018-10-13)
by Cynthia Thomas (2018-10-13)
by Christy Seeley (2018-10-13)
by Christy Seeley (2018-10-13)
by Mike Lillard (2018-10-13)
by Dominik Supple (2018-10-13)
by Dominik Supple (2018-10-13)
by Etsuko Abt (2018-10-13)
by Etsuko Abt (2018-10-13)
by Leta Clow (2018-10-13)
by Isidro Moorman (2018-10-13)
by Leta Clow (2018-10-13)
by Etsuko Abt (2018-10-13)
by Isidro Moorman (2018-10-13)
by Isidro Moorman (2018-10-13)
by Leta Clow (2018-10-13)
by Leta Clow (2018-10-14)
by Etsuko Abt (2018-10-14)
by Tesha Dykes (2018-10-14)
by Thalia McCollom (2018-10-14)
by Isidro Moorman (2018-10-14)
by Isidro Moorman (2018-10-14)
by Tesha Dykes (2018-10-14)
by Isidro Moorman (2018-10-14)
by Isidro Moorman (2018-10-14)
by Isidro Moorman (2018-10-14)
by Tesha Dykes (2018-10-14)
by Isidro Moorman (2018-10-14)
by Alfred Sisco (2018-10-14)
by Etsuko Abt (2018-10-14)
by Tesha Dykes (2018-10-14)
by Nola Strong (2018-10-14)
by Marcella Decicco (2018-10-14)
by Tamara Rountree (2018-10-14)
by Cynthia Thomas (2018-10-14)
by Mike Lillard (2018-10-15)
by Tesha Dykes (2018-10-15)
by Dominik Supple (2018-10-15)
by Katrin Bruche (2018-10-15)
by Dominik Supple (2018-10-15)
by Margret Munson (2018-10-15)
by Nola Strong (2018-10-15)
by Thalia McCollom (2018-10-15)
by Isidro Moorman (2018-10-15)
by Thalia McCollom (2018-10-15)
by Maybell Delgadillo (2018-10-15)
by Marcella Decicco (2018-10-16)
by Marcella Decicco (2018-10-16)
by Isidro Moorman (2018-10-16)
by Etsuko Abt (2018-10-16)
by Tesha Dykes (2018-10-16)
by Etsuko Abt (2018-10-16)
by Cynthia Thomas (2018-10-16)
by Etsuko Abt (2018-10-16)
by Tesha Dykes (2018-10-16)
by Thalia McCollom (2018-10-16)
by Tamara Rountree (2018-10-17)
by Tamara Rountree (2018-10-17)
by Jonelle Travers (2018-10-17)
by Wyatt Gatty (2018-10-17)
by Louisa Siemens (2018-10-17)
by Shad Queale (2018-10-17)
by Paula Howe (2018-10-17)
by Benjamin McGeorge (2018-10-17)
by Theda Creighton (2018-10-17)
by Theda Creighton (2018-10-17)
by Benjamin McGeorge (2018-10-17)
by Soila Gruber (2018-10-17)
by Nelson Streeter (2018-10-17)
by Alannah McRoberts (2018-10-17)
by Alannah McRoberts (2018-10-17)
by Benjamin McGeorge (2018-10-18)
by Jeanne Nuttall (2018-10-19)
by Meredith Wight (2018-10-19)
by Armando Shupe (2018-10-20)
by Blanca Kaufman (2018-10-21)
by Christie Santana (2020-12-11)
by Kathryn Brogan (2020-12-25)
by Katrin Bruche (2021-01-20)