Molecular Oncology

Research head:

A/Prof Ann LEE

The Programme of Molecular Oncology has partnered with clinicians, clinician-scientists and scientists from hospitals, universities, industry and research institutions across Singapore for our translational cancer research projects.

Our research focusses on:

1. The discovery of blood-based biomarkers for the early detection of breast cancer and the development of these biomarkers for use in blood-based assays. 
2. The deciphering of genetic changes associated with cancer predisposition.

Our interest in biomarker discovery has led to the identification of circulating microRNA signatures for breast cancer which can potentially be developed as blood-based assays for the early detection of breast cancer. In addition, our cancer genetic studies have identified novel genetic variations, with some being associated with increased cancer risk.

Among our key research findings, our research group has:

• Identified new breast cancer risk variants using a novel next-generation sequencing strategy 
• Identified germline variants in patients with dual breast and lung cancer, and patients with nasopharyngeal carcinoma 
• Developed polygenic risk score models for the prediction of breast cancer risk 
• Identified PALB2 mutations in our Singaporean patients and recommended that PALB2 be included in genetic testing for individuals eligible for BRCA1 and BRCA2 testing 
• Recommended that screening for the CHEK2*1100delC mutation in Asian women with a family history of breast cancer is unwarranted, in contrast to recommendations for such screening in Northern or Eastern European women 
• Reported on the identification of a BRCA1 founder mutation among Malay breast cancer patients 
• Identified circulating microRNA signatures for breast cancer detection, using blood samples

Our group has published in international journals such as Lancet Oncology, Journal of Clinical Oncology, Cancer Research, Clinical Cancer Research and Oncogene. Our research work is funded primarily by competitive grants from the National Medical Research Council (NMRC) of Singapore and Industry Alignment Funds (IAF-ICP and IAF-PP), with support from the NCC Research and Cancer Funds.

Figure 1. Strategy used for the development of a biomarker panel for breast cancer (Adapted from Cancers (Basel) (2021) 13(9):2130. doi: 10.3390/cancers13092130. PMID: 33925125)

Selected Publications (* = corresponding author)

1. Hum M, Lee ASG*. DNA methylation in breast cancer: early detection and biomarker discovery through current and emerging approaches. J Transl Med (2025) 23(1):465. Journal Impact Factor (IF): 7.52. 
2. Lee NY, Hum M, Tan GP, Seah AC, Ong PY, Kin PT, Lim CW, Samol J, Tan NC, Law HY, Tan MH, Lee SC, Ang P, Lee ASG*. Machine learning unveils an immune-related DNA methylation profile in germline DNA from breast cancer patients. Clin Epigenetics (2024) 16(1):66. IF: 7.2593. 
3. Zhang S, Wu SQY, Hum M, Perumal J, Tan EY, Lee ASG, Teng J, Dinish US, Olivo M. Complete characterization of RNA biomarker fingerprints using a multi-modal ATR-FTIR and SERS approach for label-free early breast cancer diagnosis. RSC Adv (2024) 14(5):3599-3610. IF: 4.6
4. Lee NY, Hum M, Wong M, Ong PY, Lee SC, Lee ASG*. Alleviating misclassified germline variants in underrepresented populations: a strategy using popmax. Genet Med (2024) 26(6):101124. IF: 8.8
5. Lee NY, Hum M, Zihara S, Wang L, Myint MK, Lim DW, Toh CK, Skanderup A, Samol J, Tan MH, Ang P, Lee SC, Tan EH, Lai GGY, Tan DSW, Yap YS, Lee ASG*. Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer. Hum Genomics (2023) 17(1):66. IF: 6.481
6. Zhang S, Wu QYS, Chen YF, Hum M, Wong DCL, Tan EY, Lee ASG, Teng J, U S D, Olivo M. Label-free detection of MiRNA biomarkers using broadband multi-resonant infrared metasurfaces for early breast cancer diagnosis. Nanoscale (2023) ;15(23):10057-10066. IF: 8.31
7. Lee NY, Hum M, Tan GP, Seah AC, Kin PT, Tan NC, Law HY, Lee ASG*. Degradation of methylation signals in cryopreserved DNA. Clin Epigenetics (2023) 15(1):147. IF: 7.259
8. Zou R, Loke SY, Tang YC, Too HP, Zhou L*, Lee ASG*, Hartman M. Development and validation of a circulating microRNA panel for the early detection of breast cancer. Br J Cancer (2022) 126(3):472-481. IF: 8.8
9. Lee NY, Hum M, Ong PY, Myint MK, Ong EHW, Low KP, Li Z, Goh BC, Tay JK, Loh KS, Chua MLK, Lee SC, Khor CC, Lee ASG*. Germline Variants Associated with Nasopharyngeal Carcinoma Predisposition Identified through Whole-Exome Sequencing. Cancers (Basel) (2022) 14: 3680. IF: 6.639
10. Lee NY, Hum M, Amali AA, Lim WK, Wong M, Myint MK, Tay RJ, Ong PY, Samol J, Lim CW, Ang P, Tan MH, Lee SC, Lee ASG*. Whole-exome sequencing of BRCA-negative breast cancer patients and case–control analyses identify variants associated with breast cancer susceptibility. Hum Genomics (2022) 16: 61. IF: 6.481
11. Zou R, Loke SY, Tan VK, Quek ST, Jagmohan P, Tang YC, Madhukumar P, Tan BK, Yong WS, Sim Y, Lim SZ, Png E, Lee SYS, Chan MYP, Ho TSJ, Khoo BKJ, Wong SLJ, Thng CH, Chong BK, Teo YY, Too HP, Hartman M, Tan NC, Tan EY, Lee SC, Zhou L*, Lee ASG*. Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer. Cancers (Basel) (2021) 13:2130. IF: 6.639
12. Zou R, Loke SY, Tan VK, Quek ST, Jagmohan P, Tang YC, Madhukumar P, Tan BK, Yong WS, Sim Y, Lim SZ, Png E, Lee SYS, Chan MYP, Ho TSJ, Khoo BKJ, Wong SLJ, Thng CH, Chong BK, Teo YY, Too HP, Hartman M, Tan NC, Tan EY, Lee SC, Zhou L*, Lee ASG*. Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer. Cancers (Basel) (2021) 13:2130. IF: 6.639
13. Yang X, Leslie G, Doroszuk A … Lee ASG, et al. Cancer risks associated with germline PALB2 pathogenic variants - an international study of 524 families. J Clin Oncol (2020) 38:674-685. IF: 44.544
14. Chan CHT, Munusamy P, Loke SY, Koh GL, Yang AZY, Law HY, Yoon CS, Wong CY, Yong WS, Wong NS, Ng RCH, Ong KW, Madhukumar P, Oey CL, Ho GH, Tan PH, Tan MH, Ang P, Yap YS, Lee ASG*. Evaluation of three polygenic risk score models for the prediction of breast cancer risk in Singapore Chinese. Oncotarget (2018) 9:12796–12804. IF: 5.168
15. Yap YS, Munusamy P, Lim C, Chan CHT, Prawira A, Loke SY, Lim SH, Ong KW, Yong WS, Ng SBH, Tan IBH, Callen DF, Lim JCT, Thike AA, Tan PH, Lee ASG*. Breast cancer in women with neurofibromatosis type 1 (NF1): a comprehensive case series with molecular insights into its aggressive phenotype. Breast Cancer Res and Treat (2018) 171:719-735. IF: 4.872
16. Loke SY and Lee ASG*. The future of blood-based biomarkers for the early detection of breast cancer. Eur J Cancer (2018) 92:54-68. [Review] IF: 9.162
17. Chan CHT, Munusamy P, Loke SY, Koh GL, Wong ESY, Law HY, Yoon CS, Tan MH, Yap YS, Ang P and Lee ASG*. Identification of Novel Breast Cancer Risk Loci. Cancer Res (2017) 77:5428-5437. IF: 12.531
18. Wong ESY, Shekar S, Met-Domestici M, Chan C, Sze M, Yap YS, Rozen SG, Tan MH, Ang P, Ngeow J*, Lee ASG*. Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore. npj Genom Med. (2016) 1:15003. IF: 8.617
19. Lee AS*, Ang P. Breast-cancer risk in families with mutations in PALB2. N Engl J Med (2014) 371:1650-1. [Letter]. IF: 91.245
20. Chan M, Liaw CS, Ji SM, Tan HH, Wong CY, Thike AA, Tan PH, Ho GH, Lee AS*. Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res (2013) 19:4477–4487. IF: 12.531