Whole exome sequencing of pediatric leukemia reveals a novel InDel within FLT-3 gene in AML patient from Mizo tribal population, Northeast India

Abstract

Background Leukemia is the most common type of cancer in pediatrics. Genomic mutations contribute towards the molecular mechanism of disease progression and also helps in diagnosis and prognosis. This is the first scientific mutational exploration in whole exome of pediatric leukemia patients from a cancer prone endogamous Mizo tribal population, Northeast India. Result Three non-synonymous exonic variants in NOTCH1 (p.V1699E), MUTYH (p.G143E) and PTPN11 (p.S502P) were found to be pathogenic. A novel in-frame insertion-deletion within the juxtamembrane domain of FLT3 (p.Tyr589_Tyr591delinsTrpAlaGlyAsp) was also observed. Conclusion These unique variants could have a potential mutational significance and these could be candidate genes in elucidating the possibility of predisposition to cancers within the population. This study merits further investigation for its role in diagnosis and prognosis and also suggests the need for population wide screening to identify unique mutations that might play a key role towards precision medicine.

Cancer awareness, diagnosis and treatment needs in Mizoram, India: evidence from 18 years trends (2003–2020)

“…Notable examples encompass APC, AKT1 , and CDH1 in Gastric Cancer, KRT18, CYP4A11, SLC4A3, SLC26A5, KCNS1, ABCD1, YTHDC2, PINX1, TNRC6A, TACO1, LAMA1, ACP7 and ACP7 in Type 2 Diabetes, as well as MT-ND2, MT-ND6, NOTCH1 and FLT3 in Pediatric Leukaemia patients from Mizoram. 20 , 21 , 22 , 23 , 24 , 25 These genetic deviations may owe their existence to the distinctive attributes of the population, potentially serving as pivotal research entry points for exploring potential predisposition mechanisms. As an illustration, the DPYD gene encodes DPD, a determinant governing the bioavailability of 5-Fluorouracil, thus determining treatment efficacy and toxicity for solid tumour patients.…”

Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene

“…6,7 Chromosomal translocations are often early or initiating events in leukemogenesis, and in most cases of childhood leukemias, translocations might occur before birth and in early progenitors. [8][9][10] However, chromosomal translocations are complex molecular phenomena, which are not fully understood. Chromosomal translocation is triggered by the simultaneous occurrence of double-strand DNA breaks (DSBs) in several chromosomal locations.…”

“…Of the known genetic alterations leading to leukemia, chromosomal translocations leading to the formation of the oncogenic fusion protein or oncogene activation by a new enhancer or promoter elements are among the most common rearrangements 6,7 . Chromosomal translocations are often early or initiating events in leukemogenesis, and in most cases of childhood leukemias, translocations might occur before birth and in early progenitors 8–10 . However, chromosomal translocations are complex molecular phenomena, which are not fully understood.…”