title: Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer.
abstract: OBJECTIVE
  Small cell lung cancer (SCLC) carries a poor prognosis, and the systemic therapies currently used as treatments are only modestly effective, as demonstrated by a low 5-year survival at only ∼5%. In this retrospective collected from March 2013 to study, we performed comprehensive genomic profiling of 98 small cell undifferentiated lung cancer (SCLC) samples to identify potential targets of therapy not currently searched for in routine clinical practice.
  
  
  METHODS
  DNA from 98 SCLC was sequenced to high, uniform coverage (Illumina HiSeq 2500) and analysed for all classes of genomic alterations.
  
  
  RESULTS
  A total of 386 alterations were identified for an average of 3.9 alterations per tumour (range 1–10). Fifty-two (53%) of cases harboured at least 1 actionable alteration with the potential to personalise therapy including base substitutions, amplifications or homozygous deletions in RICTOR (10%), KIT (7%), PIK3CA (6%), EGFR (5%), PTEN (5%), KRAS (5%), MCL1 (4%), FGFR1 (4%), BRCA2, (4%), TSC1 (3%), NF1 (3%), EPHA3 (3%) and CCND1. The most common non-actionable genomic alterations were alterations in TP53 (86% of SCLC cases), RB1 (54%) and MLL2 (17%).
  
  
  CONCLUSIONS
  Greater than 50% of the SCLC cases harboured at least one actionable alteration. Given the limited treatment options and poor prognosis of patients with SCLC, comprehensive genomic profiling has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease.
authors: J S
authors: JS
authors: Ross
authors: K
authors: K
authors: Wang
authors: O R
authors: OR
authors: Elkadi
authors: A
authors: A
authors: Tarasen
authors: L
authors: L
authors: Foulke
authors: C E
authors: CE
authors: Sheehan
authors: G A
authors: GA
authors: Otto
authors: G
authors: G
authors: Palmer
authors: R
authors: R
authors: Yelensky
authors: D
authors: D
authors: Lipson
authors: J
authors: J
authors: Chmielecki
authors: S M
authors: SM
authors: Ali
authors: J
authors: J
authors: Elvin
authors: D
authors: D
authors: Morosini
authors: V A
authors: VA
authors: Miller
authors: P J
authors: PJ
authors: Stephens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor