Neurofibromatosis is a neurocutaneous disorder characterized by neoplasms of the nervous system and skin.pptx

Neurofibromatosis is a neurocutaneous disorder characterized by neoplasms of the nervous system and skin


Neurofibromatosis type 1 is an autosomal dominant disease. It presents with neurofibromas, cafe-au-lait macules, freckling, and optic gliomas

1. WHOLE EXOME SEQUENCING IN BREAST CANCER COMMAND HOSPITAL, CHANDIMANDIR ABHIMANNYU CHOUDHURY

2. GENOMIC STUDIES Early identification of mutations in oncogenes and tumor suppressors Genomic landscape of cancer in an indl / community Techniques T ranscriptome sequencing of exosomal DNA and RNA Whole exome sequencing (WES) RNA-sequencing ( RNAseq ) Whole-genome sequencing (WGS) Trio exome sequencing- father, mother, child Chromatin immunoprecipitation sequencing  Comprehensive Genomic Profiling (CGP)

3. CANCER GENOME DYNAMISM Each cancer evolves with the accumulation of several types of changes Somatic/ germline mutations Copy number variation microRNA binding site polymorphism Structural variants- SNV, SNP, Indels Epigenetic factor

4. WHOLE EXOME SEQUENCING Coding region- 2% Maximum number of genetic alterations- 40-42% Depth of coverage- entire target region sequenced Cost effective- Targeted sequencing

5. AIM OF WHOLE EXOME SEQUENCING IN BREAST CANCER To identify variants in breast cancer genes associated with clinically relevant features of cancers Staging Molecular subtype Intratumoral heterogeneity Prognosis Prevalence of a variant in a family, community Prediction of response to treatment ???

6. STEPS OF WHOLE EXOME SEQUENCING DNA fragmentation Exome isolation through target capture- Cdna /BAITS Amplification and enrichment Alignment of reads Sequencing Data analysis

7. METHODS Semi conductor Pyroseq Illumina- 1-3 Mn Bp Single molecule real time seq- 30,000 Bp, 10- 20 Bn reads/ run- 87% Nanopore seq- 500kb,92-97%

8. USES OF WHOLE EXOME SEQUENCING IN BREAST CANCER Somatic aberrations across ethnic groups Classify germline coding variants to cancer risk Genotype phenotype correlation Ethnicity specific therapeutics strategies Overcome diversity and complexity of rare variants in non responders

9. SHORTCOMINGS Tissue preservation and preparation- tumor purity Indels Missense mutations Large volume Cost

10. A FEW EXAMPLES RAD52 and HSD17B14 in hereditary breast cancer susceptibility/ recurrent breast cancer in Norwegian population- Timo A Kumpala et al TP53 and TTN -strongest drivers in relation to TNBC- Clustering whole-exome sequences of breast cancer and associations with staging and molecular subtype- Kingson Man et al PTEN and FBXW7- mutations may be considered driver gene mutations for IBC-Luo et al  c.918-1G>C- enriched in hereditary BC (p = 0.006, OR 5.1, 95% CI 1.7-14.8)-North Finnish population- Sussana Koivuluoma et al

11. Manhattan plot of  z  scores from the meta-analysis assessing the association between protein-truncating variant carriers within genes and breast cancer risk- Wilcoxon et al, 2023