Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia

Al-Kzayer, Lika’a Fasih Y.; Sakashita, Kazuo; Al‐Jadiry, Mazin Faisal; Al‐Hadad, Salma Abbas; Ghali, Hasanein H.; Uyen, Le T.N.; Liu, Tingting; Matsuda, Kazuyuki; Abdulkadhim, Jaafar M.H.; Al-Shujairi, Tariq Abadi; Matti, Zead Ismael I.K.; Sughayer, Maher A.; Rihani, Rawad; Madanat, Faris; Inoshita, Toshi; Kamata, Minoru; Koike, Kenichi

doi:10.1002/pbc.25683

Cited by 23 publications

(22 citation statements)

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“…KRAS can also regulate other signaling pathways, such as PI3K-AKT, PLC-PKC, and RAL, which are also known to be involved in cancer progression [13]. KRAS is mutated in more than 20% of human cancers, mostly in pancreatic (more than 90%), colorectal and lung cancers [13] as well as leukemias [14] (Table 1). Mutations of the codons G12, G13, or Q61 are usually associated with constitutively active KRAS, and recurrent mutations in K117 and A146 seem to be additional hotspots (Figure 2).…”

Section: Gene Mutations In Pancreatic Cancermentioning

confidence: 99%

KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer

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et al. 2017

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Pancreatic cancer is a disease that has a very high fatality rate and one of the highest mortality ratios among all major cancers, remaining the fourth leading cause of cancer-related deaths in developed countries. The major treatment of pancreatic cancer is surgery; however, only 15–20% of patients are candidates for it at the diagnosis of disease. On the other hand, survival in patients, who undergo surgery, is less than 30%. In most cancers, genome stability is disturbed and pancreatic cancer is not the exception. Approximately 97% of pancreatic cancers have gene derangements, defined by point mutations, amplifications, deletions, translocations, and inversions. This review describes the most frequent genetic alterations found in pancreatic cancer.

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Section: Gene Mutations In Pancreatic Cancermentioning

confidence: 99%

KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer

Cicenas

Kvederavičiūtė

Meskinyte³

et al. 2017

Cancers

207

161

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“…The use of WES of the DBS-derived-DNA was the best approach to reach the diagnosis in our case. We previously utilized FTA cards to transfer samples of Iraqi children with acute leukemia and other hematological diseases [13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Whole-exome sequencing (WES) is an advanced approach, covers > 95% of the exons which harbor most of the genetic variants associated with phenotypes of human diseases [12]. Likewise, Flinders Technology Associates (FTA) cards are convenient for dried blood spots (DBS) archiving, transportation, DNA/RNA extraction and further genetic analysis [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

DOCK8 mutation diagnosed using whole-exome sequencing of the dried blood spot-derived DNA: a case report of an Iraqi girl diagnosed in Japan

et al. 2019

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Background: Dedicator of cytokinesis 8 (DOCK8) deficiency (MIM #243700) is a rare disease, leads to a combined primary immunodeficiency (PID), and accounts for the autosomal recessive-hyper immunoglobulin E syndrome (AR-HIES). DOCK8 deficiency status characterizes by recurrent infections, atopy, and risk of cancer. Lymphoproliferative disease complicating PID, is difficult to diagnose. Our aim is to present a rare case of PID, and to the best of our knowledge, she is the first case of DOCK8 deficiency from Iraq. The genetic diagnosis was carried out in Japan using dried blood spot-based DNA transfer and whole-exome sequencing. Case presentation: An 11-year-old Iraqi girl, of double first-cousin-parents, had a history of severe eczema, food allergy, and repeated infections. She presented with a jaw mass, bilateral cervical and axillary lymphadenopathy, and immunoglobulin (Ig) assays of 20, 3.3 and 1.7-fold above maximum normal level for age of IgE, IgA and IgG, respectively, along with a low IgM, eosinophilia and lymphopenia. Based on the jaw mass biopsy, non-Hodgkin lymphoma was suggested in Iraq, whereas histopathological re-evaluation in Japan revealed the diagnosis of a polyclonal reactive proliferation spectrum of lymphoproliferative disorders/plasmacytic hyperplasia, complicating PID. Whole-exome sequencing supported the diagnosis of PID by identifying a homozygous DOCK8 mutation with previously reported pathogenicity (NM_203447:c.3332delT, p.Phe1113Leufs*2), that may be attributed to consanguinity. Conclusions: International collaboration using an effective DNA transportation technique and next-generation sequencing was the key to pinpoint the diagnosis of DOCK8 deficiency. Our case asserted that careful pathogenetic evaluation, in an advanced setting, was crucial for ruling out the neoplastic process. Pediatricians in areas with a high prevalence of consanguinity marriage should have a high index of suspicion of DOCK8 deficiency in patients with recalcitrant eczema, and frequent respiratory and skin infectious episodes.

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“…RAS family proteins take on highly critical roles in all aspects of cell biology, serving as keys to intracellular signal transduction including cell division, differentiation, intracellular protein transport, and the organization of the cell skeleton. Point mutations, deletions and chromosomal translocations, which cause deteriorations in the RAS/ RAF/MEK/ERK pathway signaling is among the causes of Leukemia pathogenesis [16][17][18][19][20] (Table 1).…”

Section: Ras/raf/mek/erk Pathwaymentioning

confidence: 99%

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2018

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Pediatric leukemia is a multifactorial disease with an unknown etiology but can be treated. Just like many other types of cancer, genetic changes take place in leukemia. These genetic lesions, which are effective in the activation of oncogenes or inactivation of tumor suppressor genes; could lead to the development of leukemia via disruptions in the mechanisms regulating cell death, cellular differentiation or division. Studying the genetic anomalies that have not yet been determined allows treatment options that affect these steps, and thus the development of personalized treatment methods to treat chemotherapy-resistant and recurrent leukemia. This review aims to evaluate the role of RAS/RAF/MEK/ERK pathway, which was reported by previous studies to be important in development of cancer, in a pediatric leukemia subtype namely acute lymphoblastic leukemia (ALL).

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Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia

Abstract: The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement.

Cited by 23 publications

References 31 publications

KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer

KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer

DOCK8 mutation diagnosed using whole-exome sequencing of the dried blood spot-derived DNA: a case report of an Iraqi girl diagnosed in Japan

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