Skip to main content
Erschienen in: Virchows Archiv 2/2016

03.06.2016 | Original Article

Somatic mutations in histiocytic sarcoma identified by next generation sequencing

verfasst von: Qingqing Liu, Keith Tomaszewicz, Lloyd Hutchinson, Jason L. Hornick, Bruce Woda, Hongbo Yu

Erschienen in: Virchows Archiv | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20–72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 “Hotspot” oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Steven H, Swerdlow EC, Nancy LH, et al. (2008) WHO classification of tumours of haematopoietic and lymphoid tissue. IARC, Lyon Steven H, Swerdlow EC, Nancy LH, et al. (2008) WHO classification of tumours of haematopoietic and lymphoid tissue. IARC, Lyon
3.
Zurück zum Zitat Takahashi E, Nakamura S (2013) Histiocytic sarcoma: an updated literature review based on the 2008 WHO classification. J Clin Exp Hematop: JCEH 53:1–8CrossRefPubMed Takahashi E, Nakamura S (2013) Histiocytic sarcoma: an updated literature review based on the 2008 WHO classification. J Clin Exp Hematop: JCEH 53:1–8CrossRefPubMed
4.
Zurück zum Zitat Milchgrub S, Kamel OW, Wiley E, Vuitch F, Cleary ML, Warnke RA (1992) Malignant histiocytic neoplasms of the small intestine. Am J Surg Pathol 16:11–20CrossRefPubMed Milchgrub S, Kamel OW, Wiley E, Vuitch F, Cleary ML, Warnke RA (1992) Malignant histiocytic neoplasms of the small intestine. Am J Surg Pathol 16:11–20CrossRefPubMed
5.
Zurück zum Zitat Osborne BM, Mackay B (1994) True histiocytic lymphoma with multiple skin nodules. Ultrastruct Pathol 18:241–246CrossRefPubMed Osborne BM, Mackay B (1994) True histiocytic lymphoma with multiple skin nodules. Ultrastruct Pathol 18:241–246CrossRefPubMed
6.
Zurück zum Zitat Heath JL, Burgett SE, Gaca AM, Jaffe R, Wechsler DS (2014) Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy. Pediatr Blood Cancer 61:1874–1876. doi:10.1002/pbc.25100 CrossRefPubMed Heath JL, Burgett SE, Gaca AM, Jaffe R, Wechsler DS (2014) Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy. Pediatr Blood Cancer 61:1874–1876. doi:10.​1002/​pbc.​25100 CrossRefPubMed
7.
Zurück zum Zitat Tsujimura H, Miyaki T, Yamada S, Sugawara T, Ise M, Iwata S, Yonemoto T, Ikebe D, Itami M, Kumagai K (2014) Successful treatment of histiocytic sarcoma with induction chemotherapy consisting of dose-escalated CHOP plus etoposide and upfront consolidation auto-transplantation. Int J Hematol 100:507–510. doi:10.1007/s12185-014-1630-y CrossRefPubMed Tsujimura H, Miyaki T, Yamada S, Sugawara T, Ise M, Iwata S, Yonemoto T, Ikebe D, Itami M, Kumagai K (2014) Successful treatment of histiocytic sarcoma with induction chemotherapy consisting of dose-escalated CHOP plus etoposide and upfront consolidation auto-transplantation. Int J Hematol 100:507–510. doi:10.​1007/​s12185-014-1630-y CrossRefPubMed
8.
Zurück zum Zitat Gergis U, Dax H, Ritchie E, Marcus R, Wissa U, Orazi A (2011) Autologous hematopoietic stem-cell transplantation in combination with thalidomide as treatment for histiocytic sarcoma: a case report and review of the literature. J Clin Oncol 29:e251–e253. doi:10.1200/JCO.2010.32.6603 CrossRefPubMed Gergis U, Dax H, Ritchie E, Marcus R, Wissa U, Orazi A (2011) Autologous hematopoietic stem-cell transplantation in combination with thalidomide as treatment for histiocytic sarcoma: a case report and review of the literature. J Clin Oncol 29:e251–e253. doi:10.​1200/​JCO.​2010.​32.​6603 CrossRefPubMed
9.
Zurück zum Zitat Abidi MH, Tove I, Ibrahim RB, Maria D, Peres E (2007) Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant. Am J Hematol 82:932–933. doi:10.1002/ajh.20913 CrossRefPubMed Abidi MH, Tove I, Ibrahim RB, Maria D, Peres E (2007) Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant. Am J Hematol 82:932–933. doi:10.​1002/​ajh.​20913 CrossRefPubMed
10.
Zurück zum Zitat Shukla N, Kobos R, Renaud T, Teruya-Feldstein J, Price A, McAllister-Lucas L, Steinherz P (2012) Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab. Cancer 118:3719–3724. doi:10.1002/cncr.26712 CrossRefPubMed Shukla N, Kobos R, Renaud T, Teruya-Feldstein J, Price A, McAllister-Lucas L, Steinherz P (2012) Successful treatment of refractory metastatic histiocytic sarcoma with alemtuzumab. Cancer 118:3719–3724. doi:10.​1002/​cncr.​26712 CrossRefPubMed
11.
Zurück zum Zitat Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R, Cancer Genome P (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116:855–867CrossRefPubMed Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R, Cancer Genome P (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116:855–867CrossRefPubMed
12.
Zurück zum Zitat Holderfield M, Merritt H, Chan J, Wallroth M, Tandeske L, Zhai H, Tellew J, Hardy S, Hekmat-Nejad M, Stuart DD, McCormick F, Nagel TE (2013) RAF inhibitors activate the MAPK pathway by relieving inhibitory autophosphorylation. Cancer Cell 23:594–602. doi:10.1016/j.ccr.2013.03.033 CrossRefPubMed Holderfield M, Merritt H, Chan J, Wallroth M, Tandeske L, Zhai H, Tellew J, Hardy S, Hekmat-Nejad M, Stuart DD, McCormick F, Nagel TE (2013) RAF inhibitors activate the MAPK pathway by relieving inhibitory autophosphorylation. Cancer Cell 23:594–602. doi:10.​1016/​j.​ccr.​2013.​03.​033 CrossRefPubMed
14.
15.
Zurück zum Zitat Santarpia L, Qi Y, Stemke-Hale K, Wang B, Young EJ, Booser DJ, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Vidaurre T, Gomez H, Valero V, Hortobagyi GN, Symmans WF, Bottai G, Di Leo A, Gonzalez-Angulo AM, Pusztai L (2012) Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers. Breast Cancer Res Treat 134:333–343. doi:10.1007/s10549-012-2035-3 CrossRefPubMed Santarpia L, Qi Y, Stemke-Hale K, Wang B, Young EJ, Booser DJ, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Vidaurre T, Gomez H, Valero V, Hortobagyi GN, Symmans WF, Bottai G, Di Leo A, Gonzalez-Angulo AM, Pusztai L (2012) Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers. Breast Cancer Res Treat 134:333–343. doi:10.​1007/​s10549-012-2035-3 CrossRefPubMed
16.
18.
Zurück zum Zitat Suehiro Y, Wong CW, Chirieac LR, Kondo Y, Shen L, Webb CR, Chan YW, Chan AS, Chan TL, Wu TT, Rashid A, Hamanaka Y, Hinoda Y, Shannon RL, Wang X, Morris J, Issa JP, Yuen ST, Leung SY, Hamilton SR (2008) Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Clin Cancer Res 14:2560–2569. doi:10.1158/1078-0432.CCR-07-1802 CrossRefPubMedPubMedCentral Suehiro Y, Wong CW, Chirieac LR, Kondo Y, Shen L, Webb CR, Chan YW, Chan AS, Chan TL, Wu TT, Rashid A, Hamanaka Y, Hinoda Y, Shannon RL, Wang X, Morris J, Issa JP, Yuen ST, Leung SY, Hamilton SR (2008) Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Clin Cancer Res 14:2560–2569. doi:10.​1158/​1078-0432.​CCR-07-1802 CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Board RE, Ellison G, Orr MC, Kemsley KR, McWalter G, Blockley LY, Dearden SP, Morris C, Ranson M, Cantarini MV, Dive C, Hughes A (2009) Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. Br J Cancer 101:1724–1730. doi:10.1038/sj.bjc.6605371 CrossRefPubMedPubMedCentral Board RE, Ellison G, Orr MC, Kemsley KR, McWalter G, Blockley LY, Dearden SP, Morris C, Ranson M, Cantarini MV, Dive C, Hughes A (2009) Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. Br J Cancer 101:1724–1730. doi:10.​1038/​sj.​bjc.​6605371 CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, Cohen-Aubart F, Launay D, Lesot A, Mokhtari K, Canioni D, Galmiche L, Rose C, Schmalzing M, Croockewit S, Kambouchner M, Copin MC, Fraitag S, Sahm F, Brousse N, Amoura Z, Donadieu J, Emile JF (2012) High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 120:2700–2703. doi:10.1182/blood-2012-05-430140 CrossRefPubMed Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, Cohen-Aubart F, Launay D, Lesot A, Mokhtari K, Canioni D, Galmiche L, Rose C, Schmalzing M, Croockewit S, Kambouchner M, Copin MC, Fraitag S, Sahm F, Brousse N, Amoura Z, Donadieu J, Emile JF (2012) High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 120:2700–2703. doi:10.​1182/​blood-2012-05-430140 CrossRefPubMed
21.
Zurück zum Zitat Michonneau D, Kaltenbach S, Derrieux C, Trinquand A, Brouzes C, Gibault L, North MO, Delarue R, Varet B, Emile JF, Brousse N, Hermine O (2014) BRAF(V600E) mutation in a histiocytic sarcoma arising from hairy cell leukemia. J Clin Oncol 32:e117–e121. doi:10.1200/JCO.2013.49.0078 CrossRefPubMed Michonneau D, Kaltenbach S, Derrieux C, Trinquand A, Brouzes C, Gibault L, North MO, Delarue R, Varet B, Emile JF, Brousse N, Hermine O (2014) BRAF(V600E) mutation in a histiocytic sarcoma arising from hairy cell leukemia. J Clin Oncol 32:e117–e121. doi:10.​1200/​JCO.​2013.​49.​0078 CrossRefPubMed
23.
Zurück zum Zitat Go H, Jeon YK, Huh J, Choi SJ, Choi YD, Cha HJ, Kim HJ, Park G, Min S, Kim JE (2014) Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology 65:261–272. doi:10.1111/his.12416 CrossRefPubMed Go H, Jeon YK, Huh J, Choi SJ, Choi YD, Cha HJ, Kim HJ, Park G, Min S, Kim JE (2014) Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology 65:261–272. doi:10.​1111/​his.​12416 CrossRefPubMed
24.
Zurück zum Zitat Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ (2010) Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 116:1919–1923. doi:10.1182/blood-2010-04-279083 CrossRefPubMedPubMedCentral Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ (2010) Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 116:1919–1923. doi:10.​1182/​blood-2010-04-279083 CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES, Altshuler D, International SNPMWG (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–933. doi:10.1038/35057149 CrossRefPubMed Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES, Altshuler D, International SNPMWG (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–933. doi:10.​1038/​35057149 CrossRefPubMed
26.
Zurück zum Zitat Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–311CrossRefPubMedPubMedCentral Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29:308–311CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Forbes SA, Tang G, Bindal N, Bamford S, Dawson E, Cole C, Kok CY, Jia M, Ewing R, Menzies A, Teague JW, Stratton MR, Futreal PA (2010) COSMIC (the catalogue of somatic mutations in cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res 38:D652–D657. doi:10.1093/nar/gkp995 CrossRefPubMed Forbes SA, Tang G, Bindal N, Bamford S, Dawson E, Cole C, Kok CY, Jia M, Ewing R, Menzies A, Teague JW, Stratton MR, Futreal PA (2010) COSMIC (the catalogue of somatic mutations in cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Res 38:D652–D657. doi:10.​1093/​nar/​gkp995 CrossRefPubMed
29.
Zurück zum Zitat Glubb DM, Cerri E, Giese A, Zhang W, Mirza O, Thompson EE, Chen P, Das S, Jassem J, Rzyman W, Lingen MW, Salgia R, Hirsch FR, Dziadziuszko R, Ballmer-Hofer K, Innocenti F (2011) Novel functional germline variants in the VEGF receptor 2 gene and their effect on gene expression and microvessel density in lung cancer. Clin Cancer Res 17:5257–5267. doi:10.1158/1078-0432.CCR-11-0379 CrossRefPubMedPubMedCentral Glubb DM, Cerri E, Giese A, Zhang W, Mirza O, Thompson EE, Chen P, Das S, Jassem J, Rzyman W, Lingen MW, Salgia R, Hirsch FR, Dziadziuszko R, Ballmer-Hofer K, Innocenti F (2011) Novel functional germline variants in the VEGF receptor 2 gene and their effect on gene expression and microvessel density in lung cancer. Clin Cancer Res 17:5257–5267. doi:10.​1158/​1078-0432.​CCR-11-0379 CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Sen B, Peng S, Tang X, Erickson HS, Galindo H, Mazumdar T, Stewart DJ, Wistuba I, Johnson FM (2012) Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib. Sci Transl Med 4:136ra170. doi:10.1126/scitranslmed.3003513 CrossRef Sen B, Peng S, Tang X, Erickson HS, Galindo H, Mazumdar T, Stewart DJ, Wistuba I, Johnson FM (2012) Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib. Sci Transl Med 4:136ra170. doi:10.​1126/​scitranslmed.​3003513 CrossRef
33.
Zurück zum Zitat Laird AD, Christensen JG, Li G, Carver J, Smith K, Xin X, Moss KG, Louie SG, Mendel DB, Cherrington JM (2002) SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J 16:681–690. doi:10.1096/fj.01-0700com PubMed Laird AD, Christensen JG, Li G, Carver J, Smith K, Xin X, Moss KG, Louie SG, Mendel DB, Cherrington JM (2002) SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J 16:681–690. doi:10.​1096/​fj.​01-0700com PubMed
34.
Zurück zum Zitat Boyer SJ (2002) Small molecule inhibitors of KDR (VEGFR-2) kinase: an overview of structure activity relationships. Curr Top Med Chem 2:973–1000CrossRefPubMed Boyer SJ (2002) Small molecule inhibitors of KDR (VEGFR-2) kinase: an overview of structure activity relationships. Curr Top Med Chem 2:973–1000CrossRefPubMed
Metadaten
Titel
Somatic mutations in histiocytic sarcoma identified by next generation sequencing
verfasst von
Qingqing Liu
Keith Tomaszewicz
Lloyd Hutchinson
Jason L. Hornick
Bruce Woda
Hongbo Yu
Publikationsdatum
03.06.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 2/2016
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-016-1965-2

Weitere Artikel der Ausgabe 2/2016

Virchows Archiv 2/2016 Zur Ausgabe

Neu im Fachgebiet Pathologie