cancer genetics part 2

Topics in Cancer Sequencing and Genomics

• Divergent design of sequencing studies

• Sequencing technology

• Detection of mutations inc. structural rearrangements

• Cancer genome projects

• What have we learned from cancer genome sequencing?

cancer genome sequencing analysis steps

sequencing, alignment, and variant calling

consequence analysis, mutation ______,
classification of driver/passenger mutations

pathway and functional analysis

integration, visualization, and disease entered interpretation

Cancer genome sequencing:
cancer types & approach

• Cancer types
tissue specific vs pan cancer

• Approach
# samples

Matching normal and tumor tissue from a
single individual

Why not just use the published human genome sequence that is available online?

allows determining if change is related (specific) to cancer, or if the change is normally there in that individual

identify germline mut in cancer associated genes

Whole Exome Sequencing (WES)

- protein coding parts of genes (exons)
- UTR
[NO INTRONS]
- includes splicing seqs (close to exons)
More efficient and less expensive

Whole Genome Sequencing (WGS)

- Introns + Exons
- regulatory sequences
- random intergenic
[repetitive seq's difficult to analyze]

RNA-seq

Sequencing technique used to determine directly the nucleotide sequence of a collection of RNAs.

- extract mRNA (transcribed seq)
[seq} -> cDNA

Whole Genome Sequencing (WGS)
Pros & Cons

Pro - include reg seq
Con - expensive, ↓ #samples

RNA-seq
Pros & Cons

Pro
- see changes in transcription levels
- RNA editing
- altered splicing, polyadenylation

Con
- sample collection