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Genome Research publishes special issue: Cancer Genomics
Date:2/1/2012

the hands, soles of the feet, and in nail beds, and also sequenced its lymph node metastasis. By mapping the mutational landscape of the tumor and its metastasis, the study presents new genetic evidence to support the hypothesis that acral melanoma is a distinct melanoma subtype. Interestingly, although acral skin is perceived to protected from the sun, the group observed a mutational signature consistent with UV-damage.

However, until sequencing costs are low enough such that whole-genome sequencing is routine, strategies such as whole-exome sequencing, in which protein-coding genes are selectively captured and analyzed, are being employed to detect gene variants that could be driving progression of diseases such as cancer.

Wang et al. have performed whole-exome sequencing of 15 pancreatic ductal adenocarcinoma cell lines and matched normal tissue samples. Pancreatic cancer is one of the most lethal human cancers, claiming the lives of 95% of patients within five years of diagnosis. The authors describe how their study uncovered widely varying mutation rates between the cell lines, and notably, a significant correlation between loss of one copy of the MLH1 gene, involved in DNA repair, and the rate of small insertions and deletions (called "indels") in the genome of pancreatic cancer cell lines. Although loss of a copy of the chromosome region where MLH1 resides has been widely described in cancers, this is the first time that MLH1 has been associated with indel mutation rate. The whole-exome sequencing analysis showed how loss of one of the two copies of the MLH1 gene from the genome raised the rate of indel mutations ten-fold, which disrupted several well-known cancer genes, including TP53.

References:

Turajlic et al., Whole genome sequencing of matched primary and metastatic acral melanomas. Genome Res. doi:10.1101/gr.125591.111

Wang et al., Whole-exome sequencing
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Contact: Peggy Calicchia
calicchi@cshl.edu
516-422-4012
Cold Spring Harbor Laboratory
Source:Eurekalert

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