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New Genetic Tests Provide Answers for More Women


 Jennifer Ivanovich 

From the February 2010 issue of YWBCP magazine
By Jennifer Ivanovich, MS
Genetic Counselor
Washington University School of Medicine

Many young survivors have had genetic testing. Information gained from this testing is used to plan a woman’s treatment and follow-up. Recent studies have identified a significant portion of mutations that were not identified with the testing that was available for most of the last decade. Additional tools used to perform genetic testing are now available and can detect a greater number of mutations. Young survivors who have had negative genetic testing (no mutation identified) may wish to consider having this updated genetic testing performed as this testing may identify a gene mutation which had previously gone undetected. If you are considering genetic testing you will also want to know this information to ensure complete testing is performed.

Sequencing is commonly used to analyze genes for the presence of a mutation. A mutation is an abnormal alteration which disrupts the normal gene function. Sequencing detects many types of mutations but is not designed to identify all mutation types, in particular, large deletions and duplications. Consider this analogy…just as mammography cannot detect all breast cancers nor can sequencing detect all types of mutations. Multiplex ligationdependent probe amplification (MLPA) is one technique that is used to analyze genes for the presence of large deletions and duplications. Additional approaches to screen for these types of mutations are necessary and these techniques have recently been added to routine genetic testing.

Why should a woman consider additional genetic testing?

Two independent research studies extensively evaluated the BRCA1 and BRCA2 genes among people with a personal and strong family history of breast cancer and who had negative clinical genetic testing (no mutation identified ). For all of the people enrolled, gene sequencing was the primary technique used for their prior clinical genetic testing. These two studies found ~10% of people studied had a mutation that was detected using techniques other than sequencing. That is, an additional ~10% of people had a BRCA1 or BRCA2 gene mutation but were unaware of this information because their original genetic testing did not identify the mutation.

For BRCA1 and BRCA2 gene testing, if the results state one of the following, then analysis for deletion and duplication type mutations has been performed.

  • BRCA1 sequencing
    Comprehensive rearrangement
  • BRCA2 sequencing
    Comprehensive rearrangement

Or listed in a separate report as

  • BRCA1 full gene arrangement
  • BRCA2 full gene arrangement

If the report only states the following, then additional analysis for large deletions and duplications has NOT been performed:

  • BRCA1 sequencing
    5-site rearrangement panel
  • BRCA2 sequencing
These findings are not unique to the BRCA1 and BRCA2 genes. Similar studies of the e-cadherin, p53, and STK11 genes have shown a significant percentage of the mutations are deletions and duplications -- mutations not detectable with sequencing.

These studies demonstrate that when clinical genetic testing is offered, multiple techniques must be utilized in order to provide as complete analysis as is possible. It does not matter how a mutation is identified. Individuals with a mutation in any of the genes listed in this article (BRCA1, BRCA2, e-cadherin, p53, STK11) have an increased chance to develop certain types of cancer and may benefit from earlier and more frequent cancer screening.

How do I determine what testing has been performed?

  1. Contact your genetic counselor. This healthcare provider can review your testing and coordinate additional testing for you, if indicated.
  2. Check your own test results. If you have had e-cadherin, p53, or STK11 gene testing, the reporting styles vary as a number of different laboratories may perform testing for these genes. Speak with your genetic counselor to determine what techniques were used to analyze these genes.

The majority of women who have had clinical genetic testing have not had testing for deletion and duplication mutation types referenced in this article. Evaluation for these types of mutation has only recently been incorporated into routine genetic testing. Some insurance plans do not yet cover this additional analysis, however, the charge for this additional testing is less than the charge for sequencing.

It is important for young women to understand deletions and duplication mutations comprise a significant percentage of mutations in genes associated with the development of breast cancer and testing for these types of mutations was not readily available. Women diagnosed with breast cancer may take advantage of this new knowledge and consider having additional genetic testing performed. This additional testing will identify a greater number of women who have a gene mutation and who can then use this information to help plan their medical care.

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Walsh T, et al. Journal of American Medical Association. 2006, 295(12)1379-1388.

Oliveira C, et al. Human Molecular Genetics. 2009 May 1;18(9): 1545-55.