STK11 mutation status is associated with decreased survival in meningiomas

Zurück zum Zitat 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 (2013) Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet 45:285–289. https://doi.org/10.1038/ng.2526CrossRefPubMedPubMedCentral 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 (2013) Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet 45:285–289. https://​doi.​org/​10.​1038/​ng.​2526CrossRefPubMedPubMedCentral

Zurück zum Zitat Aretz S, Stienen D, Uhlhaas S et al (2005) High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat 26:513–519. https://doi.org/10.1002/humu.20253CrossRefPubMed Aretz S, Stienen D, Uhlhaas S et al (2005) High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat 26:513–519. https://​doi.​org/​10.​1002/​humu.​20253CrossRefPubMed

Zurück zum Zitat Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543–550. https://doi.org/10.1038/nature13385CrossRef Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543–550. https://​doi.​org/​10.​1038/​nature13385CrossRef

Zurück zum Zitat Guldberg P, Thor SP, Ahrenkiel V et al (1999) Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma. Oncogene 18:1777–1780. https://doi.org/10.1038/sj.onc.1202486CrossRefPubMed Guldberg P, Thor SP, Ahrenkiel V et al (1999) Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma. Oncogene 18:1777–1780. https://​doi.​org/​10.​1038/​sj.​onc.​1202486CrossRefPubMed

Zurück zum Zitat Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ, Kern SE (1999) Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 154:1835–1840. https://doi.org/10.1016/S0002-9440(10)65440-5CrossRefPubMedPubMedCentral Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ, Kern SE (1999) Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 154:1835–1840. https://​doi.​org/​10.​1016/​S0002-9440(10)65440-5CrossRefPubMedPubMedCentral

Zurück zum Zitat Qiu W, Schönleben F, Thaker HM, Goggins M, Su GH (2006) A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma. Oncogene 25:2937–2942. https://doi.org/10.1038/sj.onc.1209325CrossRefPubMedPubMedCentral Qiu W, Schönleben F, Thaker HM, Goggins M, Su GH (2006) A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma. Oncogene 25:2937–2942. https://​doi.​org/​10.​1038/​sj.​onc.​1209325CrossRefPubMedPubMedCentral

Zurück zum Zitat Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1CrossRefPubMed Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820. https://​doi.​org/​10.​1007/​s00401-016-1545-1CrossRefPubMed

Zurück zum Zitat Pain M, Wang H, Lee E et al (2018) Treatment-associated TP53 DNA-binding domain missense mutations in the pathogenesis of secondary gliosarcoma. Oncotarget 9:2603–2621. https://doi.org/10.18632/oncotarget.23517CrossRefPubMed Pain M, Wang H, Lee E et al (2018) Treatment-associated TP53 DNA-binding domain missense mutations in the pathogenesis of secondary gliosarcoma. Oncotarget 9:2603–2621. https://​doi.​org/​10.​18632/​oncotarget.​23517CrossRefPubMed

Zurück zum Zitat 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 (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data: figure 1. Cancer Discov 2:401–404. https://doi.org/10.1158/2159-8290.CD-12-0095CrossRefPubMed 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 (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data: figure 1. Cancer Discov 2:401–404. https://​doi.​org/​10.​1158/​2159-8290.​CD-12-0095CrossRefPubMed

Zurück zum Zitat Gao J, Aksoy BA, Dogrusoz U et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6. https://doi.org/10.1126/scisignal.2004088 Gao J, Aksoy BA, Dogrusoz U et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6. https://​doi.​org/​10.​1126/​scisignal.​2004088

Zurück zum Zitat Sobottka SB, Haase M, Fitze G et al (2000) Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain. J Neuro-Oncol:187–195 Sobottka SB, Haase M, Fitze G et al (2000) Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain. J Neuro-Oncol:187–195

Zurück zum Zitat Pepe F, Pisapia P, Del Basso de Caro ML et al (2019) Next generation sequencing identifies novel potential actionable mutations for grade I meningioma treatment. Histol Histopathol:18195. https://doi.org/10.14670/HH-18-195 Pepe F, Pisapia P, Del Basso de Caro ML et al (2019) Next generation sequencing identifies novel potential actionable mutations for grade I meningioma treatment. Histol Histopathol:18195. https://​doi.​org/​10.​14670/​HH-18-195

Zurück zum Zitat Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, Wilkerson MD, Fecci PE, Butaney M, Reibel JB, Soucheray M, Cohoon TJ, Janne PA, Meyerson M, Hayes DN, Shapiro GI, Shimamura T, Sholl LM, Rodig SJ, Freeman GJ, Hammerman PS, Dranoff G, Wong KK (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3:1355–1363. https://doi.org/10.1158/2159-8290.CD-13-0310CrossRefPubMed Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, Wilkerson MD, Fecci PE, Butaney M, Reibel JB, Soucheray M, Cohoon TJ, Janne PA, Meyerson M, Hayes DN, Shapiro GI, Shimamura T, Sholl LM, Rodig SJ, Freeman GJ, Hammerman PS, Dranoff G, Wong KK (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3:1355–1363. https://​doi.​org/​10.​1158/​2159-8290.​CD-13-0310CrossRefPubMed

Zurück zum Zitat Koyama S, Akbay EA, Li YY, Aref AR, Skoulidis F, Herter-Sprie GS, Buczkowski KA, Liu Y, Awad MM, Denning WL, Diao L, Wang J, Parra-Cuentas ER, Wistuba II, Soucheray M, Thai T, Asahina H, Kitajima S, Altabef A, Cavanaugh JD, Rhee K, Gao P, Zhang H, Fecci PE, Shimamura T, Hellmann MD, Heymach JV, Hodi FS, Freeman GJ, Barbie DA, Dranoff G, Hammerman PS, Wong KK (2016) STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T-cell activity in the lung tumor microenvironment. Cancer Res 76:999–1008. https://doi.org/10.1158/0008-5472.CAN-15-1439CrossRefPubMedPubMedCentral Koyama S, Akbay EA, Li YY, Aref AR, Skoulidis F, Herter-Sprie GS, Buczkowski KA, Liu Y, Awad MM, Denning WL, Diao L, Wang J, Parra-Cuentas ER, Wistuba II, Soucheray M, Thai T, Asahina H, Kitajima S, Altabef A, Cavanaugh JD, Rhee K, Gao P, Zhang H, Fecci PE, Shimamura T, Hellmann MD, Heymach JV, Hodi FS, Freeman GJ, Barbie DA, Dranoff G, Hammerman PS, Wong KK (2016) STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T-cell activity in the lung tumor microenvironment. Cancer Res 76:999–1008. https://​doi.​org/​10.​1158/​0008-5472.​CAN-15-1439CrossRefPubMedPubMedCentral

Zurück zum Zitat Liu W, Monahan KB, Pfefferle AD, Shimamura T, Sorrentino J, Chan KT, Roadcap DW, Ollila DW, Thomas NE, Castrillon DH, Miller CR, Perou CM, Wong KK, Bear JE, Sharpless NE (2012) LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma. Cancer Cell 21:751–764. https://doi.org/10.1016/j.ccr.2012.03.048CrossRefPubMedPubMedCentral Liu W, Monahan KB, Pfefferle AD, Shimamura T, Sorrentino J, Chan KT, Roadcap DW, Ollila DW, Thomas NE, Castrillon DH, Miller CR, Perou CM, Wong KK, Bear JE, Sharpless NE (2012) LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma. Cancer Cell 21:751–764. https://​doi.​org/​10.​1016/​j.​ccr.​2012.​03.​048CrossRefPubMedPubMedCentral

Zurück zum Zitat Pécuchet N, Laurent-Puig P, Mansuet-Lupo A et al (2017) Different prognostic impact of STK11 mutations in non-squamous non-small-cell lung cancer. Oncotarget 8. https://doi.org/10.18632/oncotarget.6379 Pécuchet N, Laurent-Puig P, Mansuet-Lupo A et al (2017) Different prognostic impact of STK11 mutations in non-squamous non-small-cell lung cancer. Oncotarget 8. https://​doi.​org/​10.​18632/​oncotarget.​6379

Zurück zum Zitat Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, Ali SM, Elvin JA, Singal G, Ross JS, Fabrizio D, Szabo PM, Chang H, Sasson A, Srinivasan S, Kirov S, Szustakowski J, Vitazka P, Edwards R, Bufill JA, Sharma N, Ou SI, Peled N, Spigel DR, Rizvi H, Aguilar EJ, Carter BW, Erasmus J, Halpenny DF, Plodkowski AJ, Long NM, Nishino M, Denning WL, Galan-Cobo A, Hamdi H, Hirz T, Tong P, Wang J, Rodriguez-Canales J, Villalobos PA, Parra ER, Kalhor N, Sholl LM, Sauter JL, Jungbluth AA, Mino-Kenudson M, Azimi R, Elamin YY, Zhang J, Leonardi GC, Jiang F, Wong KK, Lee JJ, Papadimitrakopoulou VA, Wistuba II, Miller VA, Frampton GM, Wolchok JD, Shaw AT, Jänne PA, Stephens PJ, Rudin CM, Geese WJ, Albacker LA, Heymach JV (2018) STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS -mutant lung adenocarcinoma. Cancer Discov 8:822–835. https://doi.org/10.1158/2159-8290.CD-18-0099CrossRefPubMedPubMedCentral Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, Ali SM, Elvin JA, Singal G, Ross JS, Fabrizio D, Szabo PM, Chang H, Sasson A, Srinivasan S, Kirov S, Szustakowski J, Vitazka P, Edwards R, Bufill JA, Sharma N, Ou SI, Peled N, Spigel DR, Rizvi H, Aguilar EJ, Carter BW, Erasmus J, Halpenny DF, Plodkowski AJ, Long NM, Nishino M, Denning WL, Galan-Cobo A, Hamdi H, Hirz T, Tong P, Wang J, Rodriguez-Canales J, Villalobos PA, Parra ER, Kalhor N, Sholl LM, Sauter JL, Jungbluth AA, Mino-Kenudson M, Azimi R, Elamin YY, Zhang J, Leonardi GC, Jiang F, Wong KK, Lee JJ, Papadimitrakopoulou VA, Wistuba II, Miller VA, Frampton GM, Wolchok JD, Shaw AT, Jänne PA, Stephens PJ, Rudin CM, Geese WJ, Albacker LA, Heymach JV (2018) STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS -mutant lung adenocarcinoma. Cancer Discov 8:822–835. https://​doi.​org/​10.​1158/​2159-8290.​CD-18-0099CrossRefPubMedPubMedCentral

Zurück zum Zitat Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur G, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34. https://doi.org/10.1056/NEJMoa1504030CrossRefPubMedPubMedCentral Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur G, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34. https://​doi.​org/​10.​1056/​NEJMoa1504030CrossRefPubMedPubMedCentral

Zurück zum Zitat Giles AJ, Hao S, Padget M et al (2019) Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK. JCI Insight 4. https://doi.org/10.1172/jci.insight.130688 Giles AJ, Hao S, Padget M et al (2019) Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK. JCI Insight 4. https://​doi.​org/​10.​1172/​jci.​insight.​130688

Zurück zum Zitat Gelerstein E, Berger A, Jonas-Kimchi T et al (2017) Regression of intracranial meningioma following treatment with nivolumab: case report and review of the literature. J Clin Neurosci 37:51–53. https://doi.org/10.1016/j.jocn.2016.11.011CrossRefPubMed Gelerstein E, Berger A, Jonas-Kimchi T et al (2017) Regression of intracranial meningioma following treatment with nivolumab: case report and review of the literature. J Clin Neurosci 37:51–53. https://​doi.​org/​10.​1016/​j.​jocn.​2016.​11.​011CrossRefPubMed

Zurück zum Zitat Dunn IF, Du Z, Touat M et al (2018) Mismatch repair deficiency in high-grade meningioma: a rare but recurrent event associated with dramatic immune activation and clinical response to PD-1 blockade. JCO Precis Oncol 2018. https://doi.org/10.1200/PO.18.00190 Dunn IF, Du Z, Touat M et al (2018) Mismatch repair deficiency in high-grade meningioma: a rare but recurrent event associated with dramatic immune activation and clinical response to PD-1 blockade. JCO Precis Oncol 2018. https://​doi.​org/​10.​1200/​PO.​18.​00190