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Genomic analysis of malaysian breast cancers unravel molecular differences from Caucasian breast cancers

Date

23 Nov 2019

Session

Poster display session

Presenters

Soo-Hwang Teo

Citation

Annals of Oncology (2019) 30 (suppl_9): ix122-ix130. 10.1093/annonc/mdz431

Authors

S. Teo1, M. Zabidi1, J.W. Pan1, P.S. Ng1, M.Y. Meng1, N. Hasan1, B. Sandey2, C.H. Yip3, P. Rajadurai4, O. Rueda2, C. Caldas5, S.F. Chin2

Author affiliations

  • 1 Breast Cancer Research Programme, Cancer Research Malaysia, 47500 - Subang Jaya/MY
  • 2 Breast Cancer Genomics, CRUK Cambridge Cancer Institute, CB1 - Cambridge/GB
  • 3 Surgery, Sime Darby Medical Centre Subang Jaya, 47500 - Subang Jaya/MY
  • 4 Pathology, Sime Darby Medical Centre Subang Jaya, 47500 - Subang Jaya/MY
  • 5 Oncology Dept., Cancer Research UK & University of Cambridge UK, CB2 0RE - Cambridge/GB
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Background

Breast cancer is the leading cause of cancer death among women, and incidence in Asia is increasing in large part because of changes in reproductive and lifestyle factors. Several appreciable differences exist between breast cancers in Asian and Caucasian women. For example, Asians have a younger median age of incidence and correspondingly, a higher prevalence of hereditary factors, and together, these suggest that they may be crucial differences at the molecular level.

Methods

We performed whole exome sequencing (WES) on 576 Malaysian breast cancers (at median coverage 75X) and their matched normal blood (40X) to detect single nucleotide variations (SNVs) and small insertions and deletions (indels). We also performed shallow whole genome sequencing (sWGS) to detect major chromosomal aberrations, and transcriptomic sequencing (RNA-seq) to measure gene expression.

Results

We captured known copy number changes, together with major breast cancer genes and their phenotypes, for example high frequency of SNVs in hotspot regions in PIK3CA and indels in GATA3. Interestingly, Malaysian breast cancer show higher prevalence of Her2+ molecular subtypes and TP53 mutations, as well as higher immune scores compared with Caucasian breast cancer cases, consistent with previous findings in other smaller Asian datasets.

Conclusions

Our report of the hitherto largest dataset of genomic profiling of Asian breast cancers show the molecular differences between Asian and Caucasian breast cancers and point to potential differences in therapy and outcome.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Cancer Research Malaysia.

Funding

Cancer Research Malaysia, Medical Research Council Newton Ungku Omar Fund, Scientex Foundation, Estee Lauder Breast Cancer Campaign, Yayasan Sime Darby, Yayasan Petronas.

Disclosure

All authors have declared no conflicts of interest.

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