Oncotarget

Research Papers:

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers

Gloria H.J. Chan, Pei Yi Ong, Jeffrey J.H. Low, Hwai Loong Kong, Samuel G.W. Ow, David S.P. Tan, Yi Wan Lim, Siew Eng Lim and Soo-Chin Lee _

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Oncotarget. 2018; 9:30649-30660. https://doi.org/10.18632/oncotarget.25769

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Abstract

Gloria H.J. Chan1,*, Pei Yi Ong1,*, Jeffrey J.H. Low2, Hwai Loong Kong1, Samuel G.W. Ow1, David S.P. Tan1,3, Yi Wan Lim1, Siew Eng Lim1 and Soo-Chin Lee1,3

1Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), Singapore

2Department of Obstetrics and Gynaecology, National University Hospital, Singapore

3Cancer Science Institute, Singapore

*These authors have contributed equally to this work

Correspondence to:

Soo-Chin Lee, email: csilsc@nus.edu.sg

Keywords: genetic testing; germ-line mutation; neoplasms; multiple primary/diagnosis

Received: May 22, 2018     Accepted: June 23, 2018     Published: July 17, 2018

ABSTRACT

Background: Developing multiple cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the clinical genetic testing outcomes of these patients.

Methods: We compared cancer index patients with ≥2 primary malignancies versus 1 primary cancer who underwent clinical evaluation and testing with multi-gene panels comprising up to 49 genes from 1998-2016.

Results: Among 1191 cancer index patients, 80.6%, 17.2%, and 2.2% respectively had 1, 2, and ≥3 primary malignancies. For patients with 2 primary cancers (n=205), the most common cancer pairs were bilateral breast (37.5%), breast-ovary (11.7%), endometrium-ovary (9.2%), colon-endometrium (3.9%) and colon-colon (3.4%). 42.3% patients underwent gene testing including 110/231 (47.6%) with multiple malignancies. Pathogenic variants were found more frequently in younger patients, in those with a family history of cancer related to the suspected syndrome, and a trend towards significance in those with multiple primary cancers (35.5% vs. 25.6%, p = 0.09). In patients with multiple cancers, pathogenic variants were most commonly identified in BRCA1 (38.5%), BRCA2 (17.9%), and the mismatch repair genes (20.5%), while 23.1% of pathogenic mutations were in other moderate- to high-penetrance cancer predisposition genes including APC, ATM, MUTYH, PALB2, RAD50 and TP53.

Conclusion: Patients with multiple cancers were more likely to carry pathogenic mutations than those with single cancer. About three-quarters of deleterious mutations in patients with multiple primary cancers were in BRCA1/2 and the mismatch repair genes, but multi-gene panel testing facilitated the detection of mutations in another 6 genes and is warranted in this high-risk population.


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