title: MMS19 as a potential predictive marker of adjuvant chemotherapy benefit in resected non-small cell lung cancer.
abstract: BACKGROUND
  Resectable non-small cell lung cancer (NSCLC) treatment options most often consist of surgical resection along with adjuvant chemotherapy (ACT). The benefit of ACT however is modest and is accompanied by important side effects.
  
  
  OBJECTIVE
  One central quest in the field is therefore the identification of a predictive marker of the response to ACT.
  
  
  METHODS
  We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort.
  
  
  RESULTS
  We identified MMS19, a component of the cytoplasmic Iron-Sulfur Assembly (CIA) machinery important for the Nucleotide Excision Repair (NER) pathway as a pivotal gene for cisplatin toxicity. We then confirmed the association between MMS19 expression and the response to Cisplatin treatment in a panel of NSCLC cell lines. Finally we validated these pre-clinical data in a subgroup of JBR.10 trial patients through a hypothesis-driven analysis, and showed that MMS19 levels associated with ACT benefit.
  
  
  CONCLUSIONS
  We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.
authors: Univ Paris-Sud, UMR-S981, Villejuif, France.|Gustave Roussy, DHU TORINO, Villejuif, France.|INSERM, U981, Villejuif, France.|Univ Paris-Sud, UMR-S981, Villejuif, France.
authors: Julien
authors: J
authors: Adam
authors: Gustave Roussy, DHU TORINO, Villejuif, France.|INSERM, U981, Villejuif, France.|Univ Paris-Sud, UMR-S981, Villejuif, France.
authors: Tony
authors: T
authors: Sourisseau
authors: Univ Paris-Sud, UMR-S981, Villejuif, France.|Gustave Roussy, DHU TORINO, Villejuif, France.|INSERM, U981, Villejuif, France.
authors: Ken A
authors: KA
authors: Olaussen
authors: Gustave Roussy, DHU TORINO, Villejuif, France.|INSERM, U981, Villejuif, France.
authors: Angélique
authors: A
authors: Robin
authors: Princess Margaret Cancer Centre, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
authors: Chang Q
authors: CQ
authors: Zhu
authors: Quinten, Paris, France.
authors: Alexandre
authors: A
authors: Templier
authors: Quinten, Paris, France.
authors: Alexandre
authors: A
authors: Civet
authors: Département Thoracique, Institut Mutualiste Montsouris, Paris, France.
authors: Philippe
authors: P
authors: Girard
authors: Gustave Roussy, DHU TORINO, Villejuif, France.
authors: Vladimir
authors: V
authors: Lazar
authors: Département Thoracique, Institut Mutualiste Montsouris, Paris, France.|Département d'Anatomie Pathologique, Institut Mutualiste Montsouris, Paris, France.
authors: Pierre
authors: P
authors: Validire
authors: Princess Margaret Cancer Centre, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
authors: Ming S
authors: MS
authors: Tsao
authors: Univ Paris-Sud, UMR-S981, Villejuif, France.|Gustave Roussy, DHU TORINO, Villejuif, France.|INSERM, U981, Villejuif, France.
authors: Jean-Charles
authors: JC
authors: Soria
authors: Univ Paris-Sud, UMR-S981, Villejuif, France.|Gustave Roussy, DHU TORINO, Villejuif, France.|INSERM, U981, Villejuif, France.
authors: Benjamin
authors: B
authors: Besse
mesh_terms: D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C416322:MMS19 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: DNA repair; Non-small-cell lung cancer; adjuvant chemotherapy