Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient

go back to reference Ali SM, Alpaugh RK, Downing SR, Stephens PJ, Yu JQ, Wu H, Buell JK, Miller VA, Lipson D, Palmer GA, Ross JS, Cristofanilli M. Response of an ERBB2-mutated inflammatory breast carcinoma to human epidermal growth factor receptor 2-targeted therapy. J Clin Oncol. 2014;32:e88–91. doi:10.1200/JCO.2013.49.0599.CrossRefPubMedPubMedCentral Ali SM, Alpaugh RK, Downing SR, Stephens PJ, Yu JQ, Wu H, Buell JK, Miller VA, Lipson D, Palmer GA, Ross JS, Cristofanilli M. Response of an ERBB2-mutated inflammatory breast carcinoma to human epidermal growth factor receptor 2-targeted therapy. J Clin Oncol. 2014;32:e88–91. doi:10.​1200/​JCO.​2013.​49.​0599.CrossRefPubMedPubMedCentral

go back to reference Anido J, Scaltriti M, Bech Serra JJ, Santiago Josefat B, Todo FR, Baselga J, Arribas J. Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J. 2006;25:3234–44. doi:10.1038/sj.emboj.7601191.CrossRefPubMedPubMedCentral Anido J, Scaltriti M, Bech Serra JJ, Santiago Josefat B, Todo FR, Baselga J, Arribas J. Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J. 2006;25:3234–44. doi:10.​1038/​sj.​emboj.​7601191.CrossRefPubMedPubMedCentral

go back to reference Arteaga CL, Engelman JA. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 2014;25:282–303. doi:10.1016/j.ccr.2014.02.025.CrossRefPubMedPubMedCentral Arteaga CL, Engelman JA. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 2014;25:282–303. doi:10.​1016/​j.​ccr.​2014.​02.​025.CrossRefPubMedPubMedCentral

go back to reference Asahina H, Yamazaki K, Kinoshita I, Yokouchi H, Dosaka-Akita H, Nishimura M. Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L. Lung Cancer. 2006;54:419–22. doi:10.1016/j.lungcan.2006.09.005.CrossRefPubMed Asahina H, Yamazaki K, Kinoshita I, Yokouchi H, Dosaka-Akita H, Nishimura M. Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L. Lung Cancer. 2006;54:419–22. doi:10.​1016/​j.​lungcan.​2006.​09.​005.CrossRefPubMed

go back to reference Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R. A functional genetic approach identifies the PI3 K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12:395–402. doi:10.1016/j.ccr.2007.08.030.CrossRefPubMed Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R. A functional genetic approach identifies the PI3 K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12:395–402. doi:10.​1016/​j.​ccr.​2007.​08.​030.CrossRefPubMed

go back to reference Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013;3:224–37. doi:10.1158/2159-8290.CD-12-0349.CrossRefPubMed Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013;3:224–37. doi:10.​1158/​2159-8290.​CD-12-0349.CrossRefPubMed

go back to reference Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4. doi:10.1158/2159-8290.CD-12-0095.CrossRefPubMed Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4. doi:10.​1158/​2159-8290.​CD-12-0095.CrossRefPubMed

go back to reference Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GMK, Factor RE, Collins LC, Allison KH, Chen Y-Y, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, Perou CM. Comprehensive molecular portraits of invasive lobular breast cancer. Cell. 2015;163:506–19. doi:10.1016/j.cell.2015.09.033.CrossRefPubMedPubMedCentral Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GMK, Factor RE, Collins LC, Allison KH, Chen Y-Y, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, Perou CM. Comprehensive molecular portraits of invasive lobular breast cancer. Cell. 2015;163:506–19. doi:10.​1016/​j.​cell.​2015.​09.​033.CrossRefPubMedPubMedCentral

go back to reference Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S, Kok CY, Jia M, De T, Teague JW, Stratton MR, McDermott U, Campbell PJ. COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2015;43:D805–11. doi:10.1093/nar/gku1075.CrossRefPubMed Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S, Kok CY, Jia M, De T, Teague JW, Stratton MR, McDermott U, Campbell PJ. COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2015;43:D805–11. doi:10.​1093/​nar/​gku1075.CrossRefPubMed

go back to reference Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1. doi:10.1126/scisignal.2004088.CrossRefPubMedPubMedCentral Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1. doi:10.​1126/​scisignal.​2004088.CrossRefPubMedPubMedCentral

go back to reference Goto T, Hirotsu Y. Analysis of tumor-derived DNA in plasma and bone marrow fluid in lung cancer patients. Med Oncol. 2016. doi:10.1007/s12032-016-0744-x. Goto T, Hirotsu Y. Analysis of tumor-derived DNA in plasma and bone marrow fluid in lung cancer patients. Med Oncol. 2016. doi:10.​1007/​s12032-016-0744-x.

go back to reference Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Mochizuki H, Omata M. Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing. Mol Genet Genomic Med. 2015;3:121–9. doi:10.1002/mgg3.120.CrossRefPubMed Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Mochizuki H, Omata M. Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing. Mol Genet Genomic Med. 2015;3:121–9. doi:10.​1002/​mgg3.​120.CrossRefPubMed

go back to reference Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Oyama T, Mochizuki H, Omata M. Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer. Mol Genet genomic Med. 2015;3:459–66. doi:10.1002/mgg3.157.CrossRefPubMedPubMedCentral Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Oyama T, Mochizuki H, Omata M. Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer. Mol Genet genomic Med. 2015;3:459–66. doi:10.​1002/​mgg3.​157.CrossRefPubMedPubMedCentral

go back to reference Hirotsu Y, Zheng T-H, Amemiya K, Mochizuki H, Guleng B, Omata M Targeted and exome sequencing identified somatic mutations in hepatocellular carcinoma. Hepatol Res. n/a–n/a 2016. doi:10.1111/hepr.12663. Hirotsu Y, Zheng T-H, Amemiya K, Mochizuki H, Guleng B, Omata M Targeted and exome sequencing identified somatic mutations in hepatocellular carcinoma. Hepatol Res. n/a–n/a 2016. doi:10.​1111/​hepr.​12663.

go back to reference Kavuri SM, Jain N, Galimi F, Cottino F, Leto SM, Migliardi G, Searleman AC, Shen W, Monsey J, Trusolino L, Jacobs SA, Bertotti A, Bose R. HER2 activating mutations are targets for colorectal cancer treatment. Cancer Discov. 2015;5:832–41. doi:10.1158/2159-8290.CD-14-1211.CrossRefPubMedPubMedCentral Kavuri SM, Jain N, Galimi F, Cottino F, Leto SM, Migliardi G, Searleman AC, Shen W, Monsey J, Trusolino L, Jacobs SA, Bertotti A, Bose R. HER2 activating mutations are targets for colorectal cancer treatment. Cancer Discov. 2015;5:832–41. doi:10.​1158/​2159-8290.​CD-14-1211.CrossRefPubMedPubMedCentral

go back to reference Koboldt DC, Fulton RS, McLellan MD Schmidt H, Kalicki-Veizer J, McMichael JF, Fulton LL, Dooling DJ, Ding L, Mardis ER, Wilson RK, Ally A, Balasundaram M, Butterfield YSN, Carlsen R, Carter C, Chu A, Chuah E, Chun H-JE, Coope RJN, Dhalla N, Guin R, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Pleasance E, Gordon Robertson A, Schein JE, Shafiei A, Sipahimalani P, Slobodan JR, Stoll D, Tam A, Thiessen N, Varhol RJ, Wye N, Zeng T, Zhao Y, Birol I, Jones SJM, Marra MA, Cherniack AD, Saksena G, Onofrio RC, Pho NH, Carter SL, Schumacher SE, Tabak B, Hernandez B, Gentry J, Nguyen H, Crenshaw A, Ardlie K, Beroukhim R, Winckler W, Getz G, Gabriel SB, Meyerson M, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Todd Auman J, Fan C, Turman YJ, Shi Y, Li L, Topal MD, He X, Chao H-H, Prat A, Silva GO, Iglesia MD, Zhao W, Usary J, Berg JS, Adams M, Booker J, Wu J, Gulabani A, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR, Balu S, Parker JS, Neil Hayes D, Perou CM, Malik S, Mahurkar S, Shen H, Weisenberger DJ, Triche Jr T, Lai PH, Bootwalla MS, Maglinte DT, Berman BP, Van Den Berg DJ, Baylin SB, Laird PW, Creighton CJ, Donehower LA, Getz G, Noble M, Voet D, Saksena G, Gehlenborg N, DiCara D, Zhang J, Zhang H, Wu C-J, Yingchun Liu S, Lawrence MS, Zou L, Sivachenko A, Lin P, Stojanov P, Jing R, Cho J, Sinha R, Park RW, Nazaire M-D, Robinson J, Thorvaldsdottir H, Mesirov J, Park PJ, Chin L, Reynolds S, Kreisberg RB, Bernard B, Bressler R, Erkkila T, Lin J, Thorsson V, Zhang W, Shmulevich I, Ciriello G, Weinhold N, Schultz N, Gao J, Cerami E, Gross B, Jacobsen A, Sinha R, Arman Aksoy B, Antipin Y, Reva B, Shen R, Taylor BS, Ladanyi M, Sander C, Anur P, Spellman PT, Lu Y, Liu W, Verhaak RRG, Mills GB, Akbani R, Zhang N, Broom BM, Casasent TD, Wakefield C, Unruh AK, Baggerly K, Coombes K, Weinstein JN, Haussler D, Benz CC, Stuart JM, Benz SC, Zhu J, Szeto CC, Scott GK, Yau C, Paull EO, Carlin D, Wong C, Sokolov A, Thusberg J, Mooney S, Ng S, Goldstein TC, Ellrott K, Grifford M, Wilks C, Ma S, Craft B, Yan C, Hu Y, Meerzaman D, Gastier-Foster JM, Bowen J, Ramirez NC, Black AD, XPATH ERROR: unknown variable ‘tname’. RE, White P, Zmuda EJ, Frick J, Lichtenberg TM, Brookens R, George MM, Gerken MA, Harper HA, Leraas KM, Wise LJ, Tabler TR, McAllister C, Barr T, Hart-Kothari M, Tarvin K, Saller C, Sandusky G, Mitchell C, Iacocca MV, Brown J, Rabeno B, Czerwinski C, Petrelli N, Dolzhansky O, Abramov M, Voronina O, Potapova O, Marks JR, Suchorska WM, Murawa D, Kycler W, Ibbs M, Korski K, Spychała A, Murawa P, Brzeziński JJ, Perz H, Łaźniak R, Teresiak M, Tatka H, Leporowska E, Bogusz-Czerniewicz M, Malicki J, Mackiewicz A, Wiznerowicz M, Van Le X, Kohl B, Viet Tien N, Thorp R, Van Bang N, Sussman H, Duc Phu B, Hajek R, Phi Hung N, Viet The Phuong T, Quyet Thang H, Zaki Khan K, Penny R, Mallery D, Curley E, Shelton C, Yena P, Ingle JN, Couch FJ, Lingle WL, King TA, Maria Gonzalez-Angulo A, Mills GB, Dyer MD, Liu S, Meng X, Patangan M, Waldman F, Stöppler H, Kimryn Rathmell W, Thorne L, Huang M, Boice L, Hill A, Morrison C, Gaudioso C, Bshara W, Daily K, Egea SC, Pegram MD, Gomez-Fernandez C, Dhir R, Bhargava R, Brufsky A, Shriver CD, Hooke J A., Leigh Campbell J, Mural RJ, Hu H, Somiari S, Larson C, Deyarmin B, Kvecher L, Kovatich AJ, Ellis MJ, King TA, Hu H, Couch FJ, Mural RJ, Stricker T, White K, Olopade O, Ingle JN, Luo C, Chen Y, Marks JR, Waldman F, Wiznerowicz M, Bose R, Chang L-W, Beck AH, Maria Gonzalez-Angulo A, Pihl T, Jensen M, Sfeir R, Kahn A, Chu A, Kothiyal P, Wang Z, Snyder E, Pontius J, Ayala B, Backus M, Walton J, Baboud J, Berton D, Nicholls M, Srinivasan D, Raman R, Girshik S, Kigonya P, Alonso S, Sanbhadti R, Barletta S, Pot D, Sheth M, Demchok JA, Mills Shaw KR, Yang L, Eley G, Ferguson ML, Tarnuzzer RW, Zhang J, Dillon L AL, Buetow K, Fielding P, Ozenberger BA, Guyer MS, Sofia HJ, Palchik JD (2012) Comprehensive molecular portraits of human breast tumours. Nature 490: 61–70. doi:10.1038/nature11412. Koboldt DC, Fulton RS, McLellan MD Schmidt H, Kalicki-Veizer J, McMichael JF, Fulton LL, Dooling DJ, Ding L, Mardis ER, Wilson RK, Ally A, Balasundaram M, Butterfield YSN, Carlsen R, Carter C, Chu A, Chuah E, Chun H-JE, Coope RJN, Dhalla N, Guin R, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Pleasance E, Gordon Robertson A, Schein JE, Shafiei A, Sipahimalani P, Slobodan JR, Stoll D, Tam A, Thiessen N, Varhol RJ, Wye N, Zeng T, Zhao Y, Birol I, Jones SJM, Marra MA, Cherniack AD, Saksena G, Onofrio RC, Pho NH, Carter SL, Schumacher SE, Tabak B, Hernandez B, Gentry J, Nguyen H, Crenshaw A, Ardlie K, Beroukhim R, Winckler W, Getz G, Gabriel SB, Meyerson M, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Todd Auman J, Fan C, Turman YJ, Shi Y, Li L, Topal MD, He X, Chao H-H, Prat A, Silva GO, Iglesia MD, Zhao W, Usary J, Berg JS, Adams M, Booker J, Wu J, Gulabani A, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR, Balu S, Parker JS, Neil Hayes D, Perou CM, Malik S, Mahurkar S, Shen H, Weisenberger DJ, Triche Jr T, Lai PH, Bootwalla MS, Maglinte DT, Berman BP, Van Den Berg DJ, Baylin SB, Laird PW, Creighton CJ, Donehower LA, Getz G, Noble M, Voet D, Saksena G, Gehlenborg N, DiCara D, Zhang J, Zhang H, Wu C-J, Yingchun Liu S, Lawrence MS, Zou L, Sivachenko A, Lin P, Stojanov P, Jing R, Cho J, Sinha R, Park RW, Nazaire M-D, Robinson J, Thorvaldsdottir H, Mesirov J, Park PJ, Chin L, Reynolds S, Kreisberg RB, Bernard B, Bressler R, Erkkila T, Lin J, Thorsson V, Zhang W, Shmulevich I, Ciriello G, Weinhold N, Schultz N, Gao J, Cerami E, Gross B, Jacobsen A, Sinha R, Arman Aksoy B, Antipin Y, Reva B, Shen R, Taylor BS, Ladanyi M, Sander C, Anur P, Spellman PT, Lu Y, Liu W, Verhaak RRG, Mills GB, Akbani R, Zhang N, Broom BM, Casasent TD, Wakefield C, Unruh AK, Baggerly K, Coombes K, Weinstein JN, Haussler D, Benz CC, Stuart JM, Benz SC, Zhu J, Szeto CC, Scott GK, Yau C, Paull EO, Carlin D, Wong C, Sokolov A, Thusberg J, Mooney S, Ng S, Goldstein TC, Ellrott K, Grifford M, Wilks C, Ma S, Craft B, Yan C, Hu Y, Meerzaman D, Gastier-Foster JM, Bowen J, Ramirez NC, Black AD, XPATH ERROR: unknown variable ‘tname’. RE, White P, Zmuda EJ, Frick J, Lichtenberg TM, Brookens R, George MM, Gerken MA, Harper HA, Leraas KM, Wise LJ, Tabler TR, McAllister C, Barr T, Hart-Kothari M, Tarvin K, Saller C, Sandusky G, Mitchell C, Iacocca MV, Brown J, Rabeno B, Czerwinski C, Petrelli N, Dolzhansky O, Abramov M, Voronina O, Potapova O, Marks JR, Suchorska WM, Murawa D, Kycler W, Ibbs M, Korski K, Spychała A, Murawa P, Brzeziński JJ, Perz H, Łaźniak R, Teresiak M, Tatka H, Leporowska E, Bogusz-Czerniewicz M, Malicki J, Mackiewicz A, Wiznerowicz M, Van Le X, Kohl B, Viet Tien N, Thorp R, Van Bang N, Sussman H, Duc Phu B, Hajek R, Phi Hung N, Viet The Phuong T, Quyet Thang H, Zaki Khan K, Penny R, Mallery D, Curley E, Shelton C, Yena P, Ingle JN, Couch FJ, Lingle WL, King TA, Maria Gonzalez-Angulo A, Mills GB, Dyer MD, Liu S, Meng X, Patangan M, Waldman F, Stöppler H, Kimryn Rathmell W, Thorne L, Huang M, Boice L, Hill A, Morrison C, Gaudioso C, Bshara W, Daily K, Egea SC, Pegram MD, Gomez-Fernandez C, Dhir R, Bhargava R, Brufsky A, Shriver CD, Hooke J A., Leigh Campbell J, Mural RJ, Hu H, Somiari S, Larson C, Deyarmin B, Kvecher L, Kovatich AJ, Ellis MJ, King TA, Hu H, Couch FJ, Mural RJ, Stricker T, White K, Olopade O, Ingle JN, Luo C, Chen Y, Marks JR, Waldman F, Wiznerowicz M, Bose R, Chang L-W, Beck AH, Maria Gonzalez-Angulo A, Pihl T, Jensen M, Sfeir R, Kahn A, Chu A, Kothiyal P, Wang Z, Snyder E, Pontius J, Ayala B, Backus M, Walton J, Baboud J, Berton D, Nicholls M, Srinivasan D, Raman R, Girshik S, Kigonya P, Alonso S, Sanbhadti R, Barletta S, Pot D, Sheth M, Demchok JA, Mills Shaw KR, Yang L, Eley G, Ferguson ML, Tarnuzzer RW, Zhang J, Dillon L AL, Buetow K, Fielding P, Ozenberger BA, Guyer MS, Sofia HJ, Palchik JD (2012) Comprehensive molecular portraits of human breast tumours. Nature 490: 61–70. doi:10.​1038/​nature11412.

go back to reference Lee JW, Soung YH, Seo SH, Kim SY, Park CH, Wang YP, Park K, Nam SW, Park WS, Kim SH, Lee JY, Yoo NJ, Lee SH. Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clin Cancer Res. 2006;12:57–61. doi:10.1158/1078-0432.CCR-05-0976.CrossRefPubMed Lee JW, Soung YH, Seo SH, Kim SY, Park CH, Wang YP, Park K, Nam SW, Park WS, Kim SH, Lee JY, Yoo NJ, Lee SH. Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clin Cancer Res. 2006;12:57–61. doi:10.​1158/​1078-0432.​CCR-05-0976.CrossRefPubMed

go back to reference Lim WK, Ong CK, Tan J, Thike AA, Ng CCY, Rajasegaran V, Myint SS, Nagarajan S, Nasir NDM, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VKM, Hartman M, Ong KW, Tan BKT, Rozen SG, Tan PH, Tan P, Teh BT. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014;46:1–6. doi:10.1038/ng.3037.CrossRef Lim WK, Ong CK, Tan J, Thike AA, Ng CCY, Rajasegaran V, Myint SS, Nagarajan S, Nasir NDM, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VKM, Hartman M, Ong KW, Tan BKT, Rozen SG, Tan PH, Tan P, Teh BT. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014;46:1–6. doi:10.​1038/​ng.​3037.CrossRef

go back to reference Mitra D, Brumlik MJ, Okamgba SU, Zhu Y, Duplessis TT, Parvani JG, Lesko SM, Brogi E, Jones FE. An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance. Mol Cancer Ther. 2009;8:2152–62. doi:10.1158/1535-7163.MCT-09-0295.CrossRefPubMed Mitra D, Brumlik MJ, Okamgba SU, Zhu Y, Duplessis TT, Parvani JG, Lesko SM, Brogi E, Jones FE. An oncogenic isoform of HER2 associated with locally disseminated breast cancer and trastuzumab resistance. Mol Cancer Ther. 2009;8:2152–62. doi:10.​1158/​1535-7163.​MCT-09-0295.CrossRefPubMed

go back to reference Murtaza M, Dawson S-J, Pogrebniak K, Rueda OM, Provenzano E, Grant J, Chin S-F, Tsui DWY, Marass F, Gale D, Ali HR, Shah P, Contente-Cuomo T, Farahani H, Shumansky K, Kingsbury Z, Humphray S, Bentley D, Shah SP, Wallis M, Rosenfeld N, Caldas C. Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat Commun. 2015;6:8760. doi:10.1038/ncomms9760.CrossRefPubMedPubMedCentral Murtaza M, Dawson S-J, Pogrebniak K, Rueda OM, Provenzano E, Grant J, Chin S-F, Tsui DWY, Marass F, Gale D, Ali HR, Shah P, Contente-Cuomo T, Farahani H, Shumansky K, Kingsbury Z, Humphray S, Bentley D, Shah SP, Wallis M, Rosenfeld N, Caldas C. Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat Commun. 2015;6:8760. doi:10.​1038/​ncomms9760.CrossRefPubMedPubMedCentral

go back to reference Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6:117–27. doi:10.1016/j.ccr.2004.06.022.CrossRefPubMed Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004;6:117–27. doi:10.​1016/​j.​ccr.​2004.​06.​022.CrossRefPubMed

go back to reference Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000;19:3159–67. doi:10.1093/emboj/19.13.3159.CrossRefPubMedPubMedCentral Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000;19:3159–67. doi:10.​1093/​emboj/​19.​13.​3159.CrossRefPubMedPubMedCentral

go back to reference Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang C-S, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Greatorex V, Ward C, Straehle C, McFadden E, Gelber RD. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–972. doi:10.1056/NEJMoa1404304.CrossRefPubMed Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang C-S, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Greatorex V, Ward C, Straehle C, McFadden E, Gelber RD. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–972. doi:10.​1056/​NEJMoa1404304.CrossRefPubMed

go back to reference Rexer BN, Arteaga Carlos L. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog. 2012;17:1–16. doi:10.1016/j.biotechadv.2011.08.021.Secreted.CrossRefPubMedPubMedCentral Rexer BN, Arteaga Carlos L. Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev Oncog. 2012;17:1–16. doi:10.​1016/​j.​biotechadv.​2011.​08.​021.​Secreted.CrossRefPubMedPubMedCentral

go back to reference Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, Arteaga CL. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res. 2007;13:4909–19. doi:10.1158/1078-0432.CCR-07-0701.CrossRefPubMed Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, Arteaga CL. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res. 2007;13:4909–19. doi:10.​1158/​1078-0432.​CCR-07-0701.CrossRefPubMed

go back to reference Robinson DR, Wu Y-M, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013;45:1446–51. doi:10.1038/ng.2823.CrossRefPubMedPubMedCentral Robinson DR, Wu Y-M, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013;45:1446–51. doi:10.​1038/​ng.​2823.CrossRefPubMedPubMedCentral

go back to reference Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84. doi:10.1056/NEJMoa052122.CrossRefPubMed Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84. doi:10.​1056/​NEJMoa052122.CrossRefPubMed

go back to reference Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L, Gray NS, Wilner K, Christensen JG, Demetri G, Shapiro GI, Rodig SJ, Eck MJ, Jänne PA. The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010;70:10038–43. doi:10.1158/0008-5472.CAN-10-2956.CrossRefPubMedPubMedCentral Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L, Gray NS, Wilner K, Christensen JG, Demetri G, Shapiro GI, Rodig SJ, Eck MJ, Jänne PA. The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010;70:10038–43. doi:10.​1158/​0008-5472.​CAN-10-2956.CrossRefPubMedPubMedCentral

go back to reference Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon Y, Cajal S, Arribas J, Baselga J. Expression of p95HER2, a truncated form of the HER2 receptor, and response to Anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99:628–38. doi:10.1093/jnci/djk134.CrossRefPubMed Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramon Y, Cajal S, Arribas J, Baselga J. Expression of p95HER2, a truncated form of the HER2 receptor, and response to Anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99:628–38. doi:10.​1093/​jnci/​djk134.CrossRefPubMed

go back to reference Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratù G, Parra JL, De Mattos-Arruda L, Grueso J, Hernández-Losa J, Arribas J, Prudkin L, Nuciforo P, Scaltriti M, Seoane J, Baselga J. Clinical response to a lapatinib-based therapy for a Li-Fraumeni Syndrome patient with a novel HER2V659E mutation. Cancer Discov. 2013;3:1238–44. doi:10.1158/2159-8290.CD-13-0132.CrossRefPubMed Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratù G, Parra JL, De Mattos-Arruda L, Grueso J, Hernández-Losa J, Arribas J, Prudkin L, Nuciforo P, Scaltriti M, Seoane J, Baselga J. Clinical response to a lapatinib-based therapy for a Li-Fraumeni Syndrome patient with a novel HER2V659E mutation. Cancer Discov. 2013;3:1238–44. doi:10.​1158/​2159-8290.​CD-13-0132.CrossRefPubMed

go back to reference Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, Wistuba II, Fong KM, Toyooka S, Shimizu N, Fujisawa T, Minna JD, Gazdar AF. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65:1642–6. doi:10.1158/0008-5472.CAN-04-4235.CrossRefPubMed Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, Wistuba II, Fong KM, Toyooka S, Shimizu N, Fujisawa T, Minna JD, Gazdar AF. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 2005;65:1642–6. doi:10.​1158/​0008-5472.​CAN-04-4235.CrossRefPubMed

go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, Mcguire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.CrossRefPubMed Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, Mcguire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.CrossRefPubMed

go back to reference Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45:1439–45. doi:10.1038/ng.2822.CrossRefPubMedPubMedCentral Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45:1439–45. doi:10.​1038/​ng.​2822.CrossRefPubMedPubMedCentral

go back to reference Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339:1546–58. doi:10.1126/science.1235122.CrossRefPubMedPubMedCentral Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339:1546–58. doi:10.​1126/​science.​1235122.CrossRefPubMedPubMedCentral

go back to reference Yuhong Lu, Xiaolin Zi Y, Zhao DM, Pollak M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (herceptin). J Natl Cancer Inst. 2001;93:1852–7.CrossRef Yuhong Lu, Xiaolin Zi Y, Zhao DM, Pollak M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (herceptin). J Natl Cancer Inst. 2001;93:1852–7.CrossRef

go back to reference Zabransky DJ, Yankaskas CL, Cochran RL, Wong HY, Croessmann S, Chu D, Kavuri SM, Red Brewer M, Rosen DM, Dalton WB, Cimino-Mathews A, Cravero K, Button B, Kyker-Snowman K, Cidado J, Erlanger B, Parsons HA, Manto KM, Bose R, Lauring J, Arteaga CL, Konstantopoulos K, Park BH. HER2 missense mutations have distinct effects on oncogenic signaling and migration. Proc Natl Acad Sci. 2015. doi:10.1073/pnas.1516853112. Zabransky DJ, Yankaskas CL, Cochran RL, Wong HY, Croessmann S, Chu D, Kavuri SM, Red Brewer M, Rosen DM, Dalton WB, Cimino-Mathews A, Cravero K, Button B, Kyker-Snowman K, Cidado J, Erlanger B, Parsons HA, Manto KM, Bose R, Lauring J, Arteaga CL, Konstantopoulos K, Park BH. HER2 missense mutations have distinct effects on oncogenic signaling and migration. Proc Natl Acad Sci. 2015. doi:10.​1073/​pnas.​1516853112.