Molecular Profiling

RESEARCH HIGHLIGHTS

MOLECULAR PROFILING A double agent The transcription factor NK2‑related Paediatric T cell acute lympho Cre to activate the expression of homeobox 1 (NKX2-1) is essential blastic leukaemia (T-ALL) is an one copy of an oncogenic Kras for normal lung development, and aggressive malignancy that is char‑ transgene and to delete Trp53 in LSL- previous work has indicated that the acterized by the presence of specific KrasG12D/+;Trp53flox/flox mice. Tracking amplification of NKX2-1 in a small genetic abnormalities; however, for genomic lentiviral integration sites subset of lung cancers is oncogenic. 40% of cases the driving mutations enabled a comparison of expression Two recent reports describe diver‑ remain undiscovered. Writing in profiles between metastatic and non- gent roles for NKX2-1 in cancer: Cancer Cell, Jules Meijerink and metastatic cells and revealed that in one context this transcription colleagues have uncovered a new Nkx2-1 is downregulated in advanced factor is oncogenic and in another it genomic profile that is associated lung adenocarcinomas. Reduced functions as a suppressor of tumour with the expression of NKX2-1. Nkx2-1 expression correlated with progression. Expression profiling and cytogenetic high-grade, poorly differentiated analysis of 117 samples from paedi‑ adenocarcinoma, whereas Nkx2-1‑ atric patients with T-ALL identified expressing tumours were well-differ‑ two mutually exclusive T-ALL entiated. Moreover, overexpression subtypes, neither of which possessed of Nkx2-1 was found to greatly limit known oncogenic alterations. One of the number of high-grade adeno these subtypes exhibited maturation carcinomas, and silencing of Nkx2-1 arrest at the CD1‑positive cortical expression in lung cancer cells either thymic stage and had high expression intravenously injected or intraspleni‑ levels of NKX2-1. Correspondingly, cally transplanted increased lung and molecular cytogenetic techniques, metastatic liver nodules, respectively. including chromatin conformation Furthermore, knockdown of Hmga2 capture on chip (4C) — a method — which is repressed by NKX2-1 — that robustly detects reciprocal in Nkx2-1‑negative cells significantly chromosomal rearrangements — in decreased metastatic seeding. this subgroup identified five NKX2-1 Thus, the dual role of NKX2-1 (or homologous NKX2-2) rearrange‑ proposed by these studies empha‑ ments in seven of 12 cases. Support sizes the importance of molecular for an oncogenic role for NKX2-1 in profiling and characterization across this study was provided by its ability not only malignancies, but also to transform fibroblast cells together their stages. with MYC or RAS. Kira Anthony, Editor, NCI-Nature However, the function of NKX2-1 Pathway Interaction Database seems to be more complex than that of a simple oncogene, as a ORIGINAL RESEARCH PAPERS Homminga, I. et al. Integrated transcript and genome analyses recent Nature paper has indicated reveal NKX2‑1 and MEF2C as potential oncogenes that Nkx2-1 can hinder lung cancer in T cell acute lymphoblastic leukemia. Cancer progression in mice. Tyler Jacks Cell 19, 484–497 (2011) | Winslow, M. M. et al. Suppression of lung adenocarcinoma progression and colleagues induced lung cancer by Nkx2‑1. Nature 473, 101–104 (2011) using lentiviral vectors expressing