RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures

Andrade, Francianne Gomes; Silva, Juliana M Furtado; Gonçalves, Bruno Alves de Aguiar; Thuler, Luiz Cláudio Santos; Barbosa, Thayana C.; Emerenciano, Mariana; Siqueira, André Machado; Pombo‐de‐Oliveira, Maria S.

doi:10.1186/1471-2407-14-133

Cited by 15 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitomycin C has remained as the only quinone-containing alkylating agent approved by the Food and Drug Administration for lung cancer treatment. Despite the overwhelming evidence suggesting importance of both NQO1 and KRAS in the pathogenesis of cancers, we are aware of only a single study investigating possible associations between them [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, possible associations between NQO1 expression and KRAS mutational status have been rarely investigated in the literature. As of February 2014, entering “KRAS” and “NQO1” into the PubMed database [ 13 ] returned only one relevant study that investigated modulation of RAS (rat sarcoma viral oncogene homolog) mutations by NQO1 [ 14 ]. Our objective was to sequence KRAS and compare expression of NQO1 as well as a panel of five clinically relevant proteins in 108 non-small cell lung carcinoma (NSCLC), the most common form of LC, patients with and without KRAS mutations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

Yılmaz

Mohamed

Patterson

et al. 2014

IJERPH

View full text Add to dashboard Cite

Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor)-targeted therapy has been used in the treatment of LC (lung cancer), mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog) driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(P)H:quinone oxidoreductase), also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin) in 108 patients with non-small cell lung carcinoma (NSCLC). NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1) oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2) selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3) since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

Yılmaz

Mohamed

Patterson

et al. 2014

IJERPH

View full text Add to dashboard Cite

show abstract

“…Studies in humans showed that prenatal exposure to air pollutants influences fetal development [ 4 ] and increases the incidence of some diseases in postnatal life [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system

et al. 2017

View full text Add to dashboard Cite

Transforming growth factor beta 1 (TGFβ1), the uteroplacental renin-angiotensin system (RAS) and vascular endothelial growth factor A (VEGF-A) participate in the placentation process. The aim of this study was to investigate the effects of exposure to pollutants on the placenta.MethodsFemale Wistar rats were exposed to filtered air (F) or to concentrated fine particulate matter (P) for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP) beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGFβ1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR.ResultsExposure to P decreased the placental mass, size, and surface area as well as the TGFβ1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII) and its receptors AT1 (AT1R) and AT2 (AT2R) were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group.ConclusionsExposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.

show abstract

“…Although former studies performed in hyperdiploid childhood leukaemia strongly indicate that RAS mut are secondary hits (Case et al , ; Davidsson et al , ), this might not be a general rule for childhood ALL. Recently, an increased risk of RAS mut was associated with maternal tobacco smoking during pregnancy [odds ratio (OR) 3·06, 95% confidence interval (CI), 1·03–9·07], and this risk was modulated by the NQO1 609CT polymorphism (OR, 4·24, 95% CI, 1·24–14·50) (Andrade et al , ).…”

mentioning

confidence: 99%

Subclonality and prenatal origin of RAS mutations in KMT2A (MLL)‐rearranged infant acute lymphoblastic leukaemia

et al. 2015

Self Cite

View full text Add to dashboard Cite

Subclonality and prenatal origin of RAS mutations in KMT2A (MLL)-rearranged infant acute lymphoblastic leukaemia KMT2A (previously termed MLL) rearrangements (KMT2A-r) constitute the most frequent aberration in infant lymphoblastic leukaemia (iALL). Mutations in the RAS genes have previously been recognized as an important somatic abnormality in KMT2A-r-iALL (Taketani et al, 2004;Liang et al, 2006;Driessen et al, 2013;Prelle et al, 2013). Certainly, KMT2A-r in iALL are present at birth (Greaves et al, 2003). On the other hand, RAS mutations (RASmut) are suggested to be secondary and subclonal hits in the leukaemogenic pathway.In this context, our study aimed to (i) quantitatively evaluate the association between RASmut at diagnosis and the main clinical features of KMT2A-r-iALL, and (ii) analyse the mutations in matched samples [neonatal blood spots, also known as Guthrie cards (Gc), remission and/or relapse]. KRAS/NRASmut were screened by direct sequencing, and mutated cases were also subjected to pyrosequencing in order to quantify the percentage of blasts harbouring the mutation. The detailed methods performed in this study are described in the Supporting Information (Data S1).Ninety-two KMT2A-r-iALL cases were included. RASmut were found in 21Á7% of cases [KRAS (14Á1%) and NRAS (7Á6%)]. In childhood ALL, RASmut have been diagnosed in 6-21% of patients (Liang et al, 2006;Wiemels et al, 2010). Recent studies in large cohorts of KMT2A-r cases have reported frequencies of 14-15% RASmut, with an even higher frequency in t(4;11) infants (c. 25%) (Driessen et al, 2013;Prelle et al, 2013). These previous data are therefore concordant with our study.The clinical-laboratory features of KMT2A-r-iALL according to RAS status are shown in Table SI. Sixty percent of RASmut patients were ≤6 months old, 60% harboured AFF1 as the KMT2A-translocation partner gene (TPG), and 80% presented both the KMT2A-AFF1 and AFF1-KMT2A transcripts at mRNA level. Although these differences were not statistically significant, these analyses are in agreement with previous data, such as a higher frequency of RASmut among younger and t(4;11) infants (Driessen et al, 2013;Prelle et al, 2013). Furthermore, KRAS (P = 0Á033) but not NRAS (P = 0Á415) mutations were associated with high white blood cell (WBC) counts.The quantitative association between RASmut at diagnosis and clinical features was analysed by pyrosequencing the mutated clones. The median percentage of mutated clones did not differ according to age group (31% vs. 27%; Fig S1A; P = 0Á43) or KMT2A-TPG (28% vs. 33%; Fig S1C; P = 0Á89). Significantly higher percentages of mutated clones were found in cases with WBC counts >300 x 10

show abstract

RAS mutations in early age leukaemia modulated by NQO1 rs1800566 (C609T) are associated with second-hand smoking exposures

Cited by 15 publications

References 40 publications

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system

Subclonality and prenatal origin of RAS mutations in KMT2A (MLL)‐rearranged infant acute lymphoblastic leukaemia

Contact Info

Product

Resources

About