2014年2月14日金曜日

膀胱癌とchromothripsis:72件の文献紹介を含めて

最近「ゲノム遺伝学的解析」が次々と進んでいるのが泌尿器領域である。
natureのオンラインであるが1月に報告されたのが↓

Nature
Received
Accepted
Published online 

Comprehensive molecular characterization of urothelial bladder carcinoma
  • Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3–TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.

もう一つ
今週号のPNASに掲載されているのが下記文献の3番目のものであるが、この論文は浸潤性膀胱癌のdeepシークエンスを行ったところ、多くの症例で例のchromothripsisを認めるというものであった。このカタストロフィックなゲノム改変イベントの最初の報告が下記文献集の71-72番、2011年お正月のCellであるから、もう3年たつのだねえ。感無量。


  • Abstract

  • Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as "stitchers," to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication-licensing complex. A second group (two bladder tumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in bladder cancer.


今回の膀胱癌の chromothripsisには少々驚いているが、この3年でchromothripsisについてどれだけの論文が出たのかまとめてみた。玉石混交であり、また総説・解説論文もまた多いが、いろんな癌腫で認められはじめているようだ。





McEvoy J, Nagahawatte P, Finkelstein D, Richards-Yutz J, Valentine M, Ma J, Mullighan C, Song G, Chen X, Wilson M, Brennan R, Pounds S, Becksfort J, Huether R, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Mardis ER, Wilson RK, Easton J, Zhang J, Downing JR, Ganguly A, Dyer MA.

Oncotarget. 2014 Jan 11.




Cai H, Kumar N, Bagheri HC, von Mering C, Robinson MD, Baudis M.

BMC Genomics. 2014 Jan 29;15(1):82.




Morrison CD, Liu P, Woloszynska-Read A, Zhang J, Luo W, Qin M, Bshara W, Conroy JM, Sabatini L, Vedell P, Xiong D, Liu S, Wang J, Shen H, Li Y, Omilian AR, Hill A, Head K, Guru K, Kunnev D, Leach R, Eng KH, Darlak C, Hoeflich C, Veeranki S, Glenn S, You M, Pruitt SC, Johnson CS, Trump DL.

Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):E672-81.




Fernandez-Banet J, Lee NP, Chan KT, Gao H, Liu X, Sung WK, Tan W, Fan ST, Poon RT, Li S, Ching K, Rejto P, Mao M, Kan Z.

Genomics. 2014 Jan 21. pii: S0888-7543(14)00004-4.




Pellestor F.

Hum Reprod. 2014 Jan 21.




Fontana P, Genesio R, Casertano A, Cappuccio G, Mormile A, Nitsch L, Iolascon A, Andria G, Melis D.

Gene. 2014 Jan 15. pii: S0378-1119(14)00038-9.


Kloosterman WP, Koster J, Molenaar JJ.

Curr Opin Oncol. 2014 Jan;26(1):64-72.




Jacoby MA, De Jesus Pizarro RE, Shao J, Koboldt DC, Fulton RS, Zhou G, Wilson RK, Walter MJ.

Leukemia. 2013 Dec 5. 


Liu G, Stevens JB, Horne SD, Abdallah BY, Ye KJ, Bremer SW, Ye CJ, Chen DJ, Heng HH.

Cell Cycle. 2013 Dec 3;13(4).


10.Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements.
Zhang CZ, Leibowitz ML, Pellman D.

Genes Dev. 2013 Dec 1;27(23):2513-30.




Markowski DN, Bullerdiek J.

N Engl J Med. 2013 Nov 28;369(22):2160.


12.Chromothripsis in uterine leiomyomas.
Mehine M, Kaasinen E, Aaltonen LA.

N Engl J Med. 2013 Nov 28;369(22):2160-1.




Pihan GA.

Front Oncol. 2013 Nov 12;3:277.




Akagi K, Li J, Broutian TR, Padilla-Nash H, Xiao W, Jiang B, Rocco JW, Teknos TN, Kumar B, Wangsa D, He D, Ried T, Symer DE, Gillison ML.

Genome Res. 2014 Feb;24(2):185-99.




Kim TM, Lee SH, Chung YJ.

World J Gastroenterol. 2013 Oct 28;19(40):6784-93.




Gu H, Jiang JH, Li JY, Zhang YN, Dong XS, Huang YY, Son XM, Lu X, Chen Z.

PLoS One. 2013 Oct 15;8(10):e76985.




Boeva V, Jouannet S, Daveau R, Combaret V, Pierre-Eugène C, Cazes A, Louis-Brennetot C, Schleiermacher G, Ferrand S, Pierron G, Lermine A, Rio Frio T, Raynal V, Vassal G, Barillot E, Delattre O, Janoueix-Lerosey I.

PLoS One. 2013 Aug 26;8(8):e72182.




Genesio R, Ronga V, Castelluccio P, Fioretti G, Mormile A, Leone G, Conti A, Cavaliere ML, Nitsch L.

Mol Cytogenet. 2013 Aug 1;6(1):29.


19.Chromothripsis under the microscope: a cytogenetic perspective of two cases of AML with catastrophic chromosome rearrangement.
Mackinnon RN, Campbell LJ.

Cancer Genet. 2013 Jun;206(6):238-51.




Nazaryan L, Stefanou EG, Hansen C, Kosyakova N, Bak M, Sharkey FH, Mantziou T, Papanastasiou AD, Velissariou V, Liehr T, Syrrou M, Tommerup N.

Eur J Hum Genet. 2013 Jul 17.




Schipler A, Iliakis G.

Nucleic Acids Res. 2013 Sep;41(16):7589-605.




Sorzano CO, Pascual-Montano A, Sánchez de Diego A, Martínez-A C, van Wely KH.

Cell Cycle. 2013 Jul 1;12(13):2016-23.




Wyatt AW, Collins CC.

J Pathol. 2013 Sep;231(1):1-3.




Mehine M, Kaasinen E, Mäkinen N, Katainen R, Kämpjärvi K, Pitkänen E, Heinonen HR, Bützow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjöberg J, Vahteristo P, Aaltonen LA.

N Engl J Med. 2013 Jul 4;369(1):43-53.




Currall BB, Chiang C, Talkowski ME, Morton CC.

Curr Genet Med Rep. 2013 Jun 1;1(2):81-90.




Hammond D, Zeng K, Espert A, Bastos RN, Baron RD, Gruneberg U, Barr FA.

J Cell Sci. 2013 Aug 1;126(Pt 15):3429-40.




Iwakawa R, Takenaka M, Kohno T, Shimada Y, Totoki Y, Shibata T, Tsuta K, Nishikawa R, Noguchi M, Sato-Otsubo A, Ogawa S, Yokota J.

Genes Chromosomes Cancer. 2013 Sep;52(9):802-16.




Krem MM, Horwitz MS.

Commun Integr Biol. 2013 May 1;6(3):e23544.




Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA.

Blood. 2013 Aug 15;122(7):1256-65.




Nagel S, Meyer C, Quentmeier H, Kaufmann M, Drexler HG, MacLeod RA.

Genes Chromosomes Cancer. 2013 Aug;52(8):741-7.




Teles Alves I, Hiltemann S, Hartjes T, van der Spek P, Stubbs A, Trapman J, Jenster G.

Hum Genet. 2013 Jun;132(6):709-13.




Bassaganyas L, Beà S, Escaramís G, Tornador C, Salaverria I, Zapata L, Drechsel O, Ferreira PG, Rodriguez-Santiago B, Tubio JM, Navarro A, Martín-García D, López C, Martínez-Trillos A, López-Guillermo A, Gut M, Ossowski S, López-Otín C, Campo E, Estivill X.

Leukemia. 2013 Dec;27(12):2376-9.




Chiarle R.

Adv Immunol. 2013;117:39-71.




Landry JJ, Pyl PT, Rausch T, Zichner T, Tekkedil MM, Stütz AM, Jauch A, Aiyar RS, Pau G, Delhomme N, Gagneur J, Korbel JO, Huber W, Steinmetz LM.

G3 (Bethesda). 2013 Aug 7;3(8):1213-24.




Wyatt AW, Mo F, Wang Y, Collins CC.

Asian J Androl. 2013 May;15(3):301-8.




Korbel JO, Campbell PJ.

Cell. 2013 Mar 14;152(6):1226-36.




Kloosterman WP, Cuppen E.

Curr Opin Cell Biol. 2013 Jun;25(3):341-8.




Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM.

Genome Res. 2013 May;23(5):762-76.




Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G, Ligon KL, Palescandolo E, Van Hummelen P, Ducar MD, Raza A, Sunkavalli A, Macconaill LE, Stemmer-Rachamimov AO, Louis DN, Hahn WC, Dunn IF, Beroukhim R.

Nat Genet. 2013 Mar;45(3):285-9.




Donley N, Thayer MJ.

Semin Cancer Biol. 2013 Apr;23(2):80-9.




Hirsch D, Kemmerling R, Davis S, Camps J, Meltzer PS, Ried T, Gaiser T.

Cancer Res. 2013 Mar 1;73(5):1454-60.




Wang E.

Cancer Lett. 2013 Nov 1;340(2):261-9.




Jones MJ, Jallepalli PV.

Dev Cell. 2012 Nov 13;23(5):908-17




Holland AJ, Cleveland DW.

Nat Med. 2012 Nov;18(11):1630-8.




Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ.

Genome Res. 2013 Feb;23(2):217-27.




Poot M.

Mol Syndromol. 2012 Sep;3(3):99-101.




Arlt MF, Rajendran S, Birkeland SR, Wilson TE, Glover TW.

PLoS Genet. 2012 Sep;8(9):e1002981.




Shibata T.

Pathol Int. 2012 Oct;62(10):647-59.




Forment JV, Kaidi A, Jackson SP.

Nat Rev Cancer. 2012 Oct;12(10):663-70.




Wu C, Wyatt AW, McPherson A, Lin D, McConeghy BJ, Mo F, Shukin R, Lapuk AV, Jones SJ, Zhao Y, Marra MA, Gleave ME, Volik SV, Wang Y, Sahinalp SC, Collins CC.

Genes Chromosomes Cancer. 2012 Dec;51(12):1144-53.




Inaki K, Liu ET.

Trends Genet. 2012 Nov;28(11):550-9.




Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stütz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fèvre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognár L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD.

Nature. 2012 Aug 2;488(7409):49-56.




Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Poot M, Cuppen E.

Cell Rep. 2012 Jun 28;1(6):648-55.




Righolt C, Mai S.

Genes Chromosomes Cancer. 2012 Nov;51(11):975-81.




Lapuk AV, Wu C, Wyatt AW, McPherson A, McConeghy BJ, Brahmbhatt S, Mo F, Zoubeidi A, Anderson S, Bell RH, Haegert A, Shukin R, Wang Y, Fazli L, Hurtado-Coll A, Jones EC, Hach F, Hormozdiari F, Hajirasouliha I, Boutros PC, Bristow RG, Zhao Y, Marra MA, Fanjul A, Maher CA, Chinnaiyan AM, Rubin MA, Beltran H, Sahinalp SC, Gleave ME, Volik SV, Collins CC.

J Pathol. 2012 Jul;227(3):286-97.




Liu P, Carvalho CM, Hastings PJ, Lupski JR.

Curr Opin Genet Dev. 2012 Jun;22(3):211-20.



Chiang C, Jacobsen JC, Ernst C, Hanscom C, Heilbut A, Blumenthal I, Mills RE, Kirby A, Lindgren AM, Rudiger SR, McLaughlan CJ, Bawden CS, Reid SJ, Faull RL, Snell RG, Hall IM, Shen Y, Ohsumi TK, Borowsky ML, Daly MJ, Lee C, Morton CC, MacDonald ME, Gusella JF, Talkowski ME.

Nat Genet. 2012 Mar 4;44(4):390-7, S1.




Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, Ebus ME, Haneveld F, Lakeman A, Schild L, Molenaar P, Stroeken P, van Noesel MM, Ora I, Santo EE, Caron HN, Westerhout EM, Versteeg R.

Nature. 2012 Feb 22;483(7391):589-93.




Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino DM, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker FG, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO.

Cell. 2012 Jan 20;148(1-2):59-71.




Maher CA, Wilson RK.

Cell. 2012 Jan 20;148(1-2):29-32.




Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D.

Nature. 2012 Jan 18;482(7383):53-8.




García Sagredo JM.

An R Acad Nac Med (Madr). 2012;129(2):627-40; discussion 641. Spanish.




Pei J, Jhanwar SC, Testa JR.

Leuk Res Rep. 2012 Jan 1;1(1):4-6.




Chen JM, Férec C, Cooper DN.

Mutat Res. 2012 Jan-Mar;750(1):52-9.




Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E.

Genome Biol. 2011 Oct 19;12(10):R103.




Liu P, Erez A, Nagamani SC, Dhar SU, Kołodziejska KE, Dharmadhikari AV, Cooper ML, Wiszniewska J, Zhang F, Withers MA, Bacino CA, Campos-Acevedo LD, Delgado MR, Freedenberg D, Garnica A, Grebe TA, Hernández-Almaguer D, Immken L, Lalani SR, McLean SD, Northrup H, Scaglia F, Strathearn L, Trapane P, Kang SH, Patel A, Cheung SW, Hastings PJ, Stankiewicz P, Lupski JR, Bi W.

Cell. 2011 Sep 16;146(6):889-903.




Colnaghi R, Carpenter G, Volker M, O'Driscoll M.

Semin Cell Dev Biol. 2011 Oct;22(8):875-85.




Stevens JB, Abdallah BY, Liu G, Ye CJ, Horne SD, Wang G, Savasan S, Shekhar M, Krawetz SA, Hüttemann M, Tainsky MA, Wu GS, Xie Y, Zhang K, Heng HH.

Cell Death Dis. 2011 Jun 30;2:e178.




Magrangeas F, Avet-Loiseau H, Munshi NC, Minvielle S.

Blood. 2011 Jul 21;118(3):675-8.




Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijn E, Bakker SC, Letteboer T, van Nesselrooij B, Hochstenbach R, Poot M, Cuppen E.

Hum Mol Genet. 2011 May 15;20(10):1916-24.




Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ.

Cell. 2011 Jan 7;144(1):27-40.




Meyerson M, Pellman D.

Cell. 2011 Jan 7;144(1):9-10.


0 件のコメント: