Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia  

Oleh:

Mullighan, Charles G. ; Goorha, Salil ; Radtke, Ina ; Miller, Christopher B. ; Caustan-Smith, Elaine ; Dalton, James D ; Girtman, Kevin ; Mathew, Susan ; Jing Ma ; Pounds, Stanley B. ; Su, Xiaoping ; Pui, Ching-Hon ; Relling, Mary V. ; Evans, William E. ; Shurtleff, Sheila A ; Downing, James R.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: NATURE (keterangan: ada di Proquest) vol. 446 no. 7137 (Apr. 2007), page 758.

Ketersediaan

Perpustakaan FK Nomor Panggil: N01.K.2007.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAXS gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAXS mutations resulted in reduced levels of PAXS protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, /KZF1 (lKAROS) and /KZF3 (A/OLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.

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