Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes Among Korean Breast Cancer Patients. - PubMed - NCBI

Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes Among Korean Breast Cancer Patients. - PubMed - NCBI

Cancer Res Treat. 2016 Sep 13. doi: 10.4143/crt.2016.292. [Epub ahead of print]

Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes Among Korean Breast Cancer Patients.

Yoon KA1,2, Park B3, Lee BI4, Yang MJ1, Kong SY5,6,7, Lee ES1,6,8.

Author information

Abstract

PURPOSE:

Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. The aim of study is to identify potentially pathogenic unclassified variants by comparing their prevalence between breast cancer patients and controls.

METHODS:

A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency. Candidate variants were genotyped in 421 healthy controls. We also examined family members of study participants. The effects of amino acid substitutions on protein structure and function were predicted by in silico tools.

RESULTS:

Genetic test detected 33 unclassified variants in BRCA1 and 47 in BRCA2. Among fifteen candidates that were genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 did not detected in healthy controls. The c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. The average age at diagnosis for four patients harboring the c.5339T>C variant was 34. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal (BRCT) domain was predicted to have an effect on BRCA1 protein structure/function.

CONCLUSION:

This study showed that a comparison of genotype frequency between cases and controls could help identify potentially pathogenic unclassified variants of BRCA genes. Our findings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their family.

KEYWORDS:

BRCA1; BRCA2; Familial breast cancer; Unclassified variants

PMID:

 

27658390

 

DOI:

 

10.4143/crt.2016.292

[PubMed - as supplied by publisher] 

Free full text

Public Health Genomics Knowledge Base (v1.2)






Last Updated: Sep 29, 2016

• BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis.
  Zhu Yaning, et al. Oncotarget 2016 9
• Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes Among Korean Breast Cancer Patients.
  Yoon Kyong-Ah, et al. Cancer research and treatment : official journal of Korean Cancer Association 2016 9
• Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening.
  Paluch-Shimon S et al. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2016 Sep 27(suppl 5) v103-v110
• BRCA Share 
• BRCA Share: A Collection of Clinical BRCA Gene Variants.
  Beroud Christophe et al. Human mutation 2016 Sep
• Occult and subsequent cancer incidence following risk-reducing surgery in BRCA mutation carriers.
  Zakhour Mae, et al. Gynecologic oncology 2016 9
• Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial.
  Ledermann Jonathan A, et al. The Lancet. Oncology 2016 9
• Want A BRCA Test? Some Insurers Require Genetic Counseling First
  M Andrews, NPR, September 14, 2016
• Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
  Kotsopoulos Joanne et al. Journal of the National Cancer Institute 2017 Jan 109(1)
• Finding all BRCA pathogenic mutation carriers: best practice models.
  Hoogerbrugge Nicoline et al. European journal of human genetics : EJHG 2016 Sep S19-26
• Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.
  Secrier Maria, et al. Nature genetics 2016 9
• BRCA testing within the Department of Veterans Affairs: concordance with clinical practice guidelines.
  Chun Danielle S et al. Familial cancer 2016 Sep
• Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial.
  Metcalfe Kelly A et al. Genetics in medicine : official journal of the American College of Medical Genetics 2016 Sep
• Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma.
  Morse Christopher B, et al. Gynecologic oncology 2016 8
• BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype.
  Al-Shamsi Humaid O, et al. Journal of gastrointestinal oncology 2016 8 (4) 556-61

• CDC Information (4)
• CDC-Authored Pub (2)

• Human (47)
• Pathogen (0)

• Human (485)
• Pathogen (0)

• Human (141)
• Pathogen (0)

• Guidelines (7)
• Tier Table (3)
• Synthesis (7)

• Huamn (27)
• Pathogen (0)

Relevant Resources

• Cancer Genomics and Epidemiology Navigator (CGEN)
• Genetics and Genomics Competencies Center (G2C2)
• NIH Genetic Testing Registry
• NIH MedGen Database
• Online Mendelian Inheritance in Man (OMIM)
• PharmGKB