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Pediatr Blood Cancer. 2018 Feb;65(2). doi: 10.1002/pbc.26786. Epub 2017 Aug 29.

Mutational status of NRAS, KRAS, and PTPN11 genes is associated with genetic/cytogenetic features in children with B-precursor acute lymphoblastic leukemia.

Author information

1
Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
2
Division of Hematology-Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Abstract

BACKGROUND:

We aimed to investigate the frequencies and the association with genetic/cytogenetic abnormalities as well as prognostic relevance of RAS pathway mutations in Taiwanese children with B-precursor acute lymphoblastic leukemia (ALL), the largest cohort in Asians.

PROCEDURE:

Between 1995 and 2012, marrow samples at diagnosis from 535 children were studied for NRAS, KRAS, and PTPN11 mutations. The mutational status of each gene was correlated with the clinico-hematological features, recurrent genetic abnormalities, and outcomes for those treated with TPOG-ALL-2002 protocol (n = 346).

RESULTS:

The frequencies of NRAS, KRAS, and PTPN11 mutations were 10.8% (57/530), 10.2% (54/530), and 3.0% (16/526), respectively. NRAS mutations were associated with a higher frequency of hyperdiploidy (P = 0.01) and lower frequency of ETV6-RUNX1 (P < 0.01), whereas KRAS mutations were associated with younger age (P < 0.01), a higher frequency of KMT2A rearranged (P < 0.01) but no significant difference if infants with ALL were excluded, and inferior event-free survival (66.6% vs. 80.5%, P = 0.04). None of patients with TCF3-PBX1 had KRAS mutation (P = 0.02).

CONCLUSIONS:

Our study showed that the frequency of KRAS mutations in Taiwan was significantly higher than that reported in Caucasians. The occurrence of RAS pathway mutations was associated with recurrent genetic/cytogenetic abnormalities in pediatric B-precursor ALL.

KEYWORDS:

KRAS; NRAS; PTPN11 mutation; pediatric acute lymphoblastic leukemia

PMID:
28853218
DOI:
10.1002/pbc.26786
[Indexed for MEDLINE]

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