ABSTRACT
Background: Molecular analyses in hematological malignancies provide insights about genetic makeup. Probable etiological factors in leukemogenesis could also be disclosed. Since genetic analyses are still primitive in Iraq, a country of repeated wars, we conceived of performing next-generation sequencing (NGS), to disclose the genomic landscape of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among a cohort of Iraqi children. Methods: Dried blood samples were collected from Iraqi children with ALL (n=55), or AML (n=11), and transferred to Japan where NGS was done. Whole-exome, whole-genome, and targeted gene sequencings were performed. Results: Somatic point mutations and the copy number variations among Iraqi children with acute leukemia were comparable with those in other countries, and cytosine-to-thymine nucleotide alterations were dominant. Strikingly, TCF3-PBX1 was the most recurrent fusion gene (22.4%) in B-cell precursor ALL (B-ALL), and acute promyelocytic leukemia (AML-M3) was subtyped in 5 AML cases. Additionally, a high frequency of RAS signaling pathway mutations was detected in children with B-ALL (38.8%), along with 3 AML cases that carried oncogenic RAS. Conclusions: Apart from disclosing the high frequency of TCF3-PBX1, NGS confirmed our previous finding of recurrent RAS mutations in Iraqi childhood acute leukemia. Our results suggest that the biology of Iraqi childhood acute leukemia is in part characteristic, where the war-aftermath environment or geography might play a role.
ABSTRACT
Congenital mesoblastic nephroma (CMN) is a rare tumor, yet it is the most frequently diagnosed renal neoplasm in the first 3 months of life. CMN reports with prenatal magnetic resonance imaging (MRI) are scarce. Our aims were to describe a case with fetal MR imaging along with other findings, and to review the literature concerned with prenatal MRI detection of CMN. Upon routine ultrasound (US) examination of a 36-week pregnant woman, a fetal abdominal mass was disclosed. Prenatal MRI revealed a large, well-circumscribed renal mass of solid and cystic components, not invading the adjacent tissues, but compressing normal renal parenchyma of the lower pole of the left kidney. Thus, a low malignant renal tumor was considered. After Cesarean delivery, imaging including US and computerized tomography (CT) scan was performed on the apparently healthy boy and verified the prenatal MRI finding. Accordingly, left nephrectomy was performed at the age of 12 days. The pathology confirmed CT results of the solid and cystic components of the mass, in addition to the necrotic and hemorrhagic constitution. Cellular CMN was diagnosed, and ETV6 gene rearrangement was demonstrated by FISH analysis. No recurrence was detected within the 40 months follow-up after the operation. Our report described a rare and seldomly detected renal tumor in utero with the aid of MRI and reviewed the few related reports in the literature in which MRI was performed prenatally. This report also highlights the need for prenatal MRI as a complementary tool to US in cases with suspected fetal renal mass and recommends its use for carefully managing the possible risks during the perinatal period.
ABSTRACT
BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. To guide and streamline therapy in the war-torn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population. METHODS: Next-generation sequencing of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled. RESULTS: Mutations were detected in previously described WT "hot spots" (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range 6-78 months). CONCLUSIONS: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.
