MEDICAL GENETICS AND PEDIATRIC ONCOLOGY IN CONGENITAL CANCER SYNDROMES

Abstract

Pediatric oncology deals with congenital cancer syndromes. They are usually manifested by germline abnormalities which predispose children to cancer in the early ages.  This work was aimed at clarifying the genetic and clinical landscapes of these diseases through the mixed-methods approach.  We performed whole exome sequencing and comparative genomic hybridization on cohort of children with tumors including retinoblastoma, Wilms tumor and Li-Fraumeni syndrome. This was a quantitative study.  Bayesian inference identified statistically significant associations between gene changes and some cancer features in TP53, RB1, WT1 and NF1.  Meanwhile, the qualitative interviews with the caregivers and the doctors revealed the patterns of the ways genetic traits are inherited and the ways they may vary, the ways they influence the mental state of people.  According to KaplanMeier survival curves and the Cox regression, a reduction of the prognosis importance was noted in terms of mutation zygosity and the syndromic features.  The unsupervised clustering and principal component analysis assisted to group patients with different clinical-genomic characteristics further.  This discovery supports a new form of categorization using genetic and clinical information to enhance precision of diagnosis and risk-stratification.  The study demonstrates the usefulness of integrating genetics with clinical data used in the real world process of providing treatments on cancerous children in order to personalize them.  The implications of our findings are huge regarding the process of finding congenital cancer syndromes at an early age and monitoring them as well as treating them.