RT Journal Article
SR Electronic
T1 Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 772
OP 776
DO 10.1136/jclinpath-2014-202447
VO 67
IS 9
A1 J S Ross
A1 K Wang
A1 O R Elkadi
A1 A Tarasen
A1 L Foulke
A1 C E Sheehan
A1 G A Otto
A1 G Palmer
A1 R Yelensky
A1 D Lipson
A1 J Chmielecki
A1 S M Ali
A1 J Elvin
A1 D Morosini
A1 V A Miller
A1 P J Stephens
YR 2014
UL http://jcp.bmj.com/content/67/9/772.abstract
AB Aims 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.