Penn State Cancer Institute

This webpage will help keep you informed of new developments in the field of clinical cancer genetics. Some of these new developments reflect an improvement to an existing test that may have the ability to detect more mutations than the test previously offered. Other developments listed on the webpage may serve to announce the availability of a new genetic test that would not have been offered at the time of one’s initial cancer genetics evaluation. This webpage will be updated as needed to highlight new developments in the field. It is not meant to take the place of a consultation with a cancer genetics professional. If there are any questions, please do not hesitate to call your local cancer genetics professional. To locate a cancer genetics professional in your area, go to the National Society of Genetic Counselors website or you can search the National Cancer Institute’s Cancer Genetics Services Directory. The Penn State Cancer Genetics Program can be reached by calling 717-531-1631.

2/06/2007 Updates and Modifications made to Cancer Genetics Program and Website

The Penn State Cancer Institute is proud to announce updates and modifications to the Penn State Cancer Genetics Program and its developing section on the PSCI website. An article written by Matthew Solovey, Strategic Services representative for the Penn State Milton S. Hershey Medical Center, details the findings of a group of researchers dedicated to improving genetic counseling. These researchers include Dana T. Kausmeyer, M.D.; Eugene J. Lengerich, V.M.D., M.S.; Brenda C. Kluhsman, M.S.S., Ph.D.; Dorothy Morrone, R.N.; Gregory R. Harper, M.D., Ph.D.; and Maria J. Baker, Ph.D. The findings of the study were published in the December issue of Journal of Genetic Counseling.

Click here to view Mr. Solovey's article.

8/1/2006 Further Enhancement to Genetic Testing of the BRCA1 / BRCA2 Genes

Genetic testing of the BRCA1 and BRCA2 genes became available on a clinical basis in 1996 and initially consisted solely of proofreading or sequencing both genes. The genetic test was first enhanced in August 2002 to include screening for 5 large mutations in the BRCA1 gene that would be missed by proofreading or sequencing the genes. This additional part of the test was referred to as the 5-site rearrangement panel and was estimated to detect approximately half of the 7 to 15% of mutations missed by sequencing. On 8/1/06, a new technology called the BRACAnalysis® Rearrangement Test (BART) became available. This test uses quantitative PCR to detect large rearrangements in both the BRCA1 and BRCA2 genes and is estimated to detect the majority of the remaining mutations in the BRCA1 and BRCA2 genes. BART will be available for no additional charge to those patients who pursued Comprehensive BRACAnalysis® on or after 8/1/06 in which no mutation was detected or a genetic variant was identified if they meet the following family history criteria:

Patient NOT positive for a deleterious mutation by BRACAnalysis® AND affected with:	Additional Family History Required:
Breast cancer before age 50	2 or more relatives with breast cancer before age 50 and/or ovarian cancer at any age*
Ovarian cancer at any age	2 or more relatives with breast cancer before age 50 and/or ovarian cancer at any age*
Male breast cancer at any age	2 or more relatives with breast cancer before age 50 and/or ovarian cancer at any age*
Breast cancer at or after age 50 and ovarian cancer at any age	1 or more relatives with breast cancer before age 50 and/or ovarian cancer at any age*
Breast cancer before age 50 and ovarian cancer at any age	No additional relatives required
Patients with a known large rearrangement in their family

*At least one relative must be a first or second-degree relative

Studies have shown that approximately 8.8% of individuals who meet the above family history criteria will have a mutation detected by BART. In contrast, only 1% of families who do not meet the family history criteria will have a mutation detected by BART. BART is also available to individuals who do not meet the family history criteria or who were tested prior to July 31, 2006 for an additional cost of $650.

2/23/2006 CHEK2 Genetic Testing Becomes Available for Families With a History of Breast Cancer, Prostate Cancer or Who Have Features Characteristic of Li-Fraumeni or Li-Fraumeni-like Syndrome

A specific mutation in the CHEK2 gene has been identified that appears to double or possibly triple a woman’s risk to develop breast cancer and may increase a man’s risk for breast cancer by ten-fold. In addition, mutations in the CHEK2 gene have been found in families with both sporadic and familial prostate cancer, as well as some families with Li-Fraumeni or Li-Fraumeni-like syndrome. Possible indications for testing include 1) women with first degree relatives with bilateral breast cancer, 2) individuals with a family history of breast cancer with no mutation detected in the BRCA1 and BRCA2 genes, 3) individuals with either sporadic or familial prostate cancer, 4) individuals who may have either Li-Fraumeni syndrome or Li-Fraumeni-like syndrome without a mutation detected in the p53 gene, and 5) if a CHEK2 mutation has been identified in an affected family member. This testing has only recently become available on a clinical basis and as such, there is ongoing discussion amongst cancer genetics professionals as to when and under which circumstances it should be offered.

1/1/2005 New Genetic Test for HNPCC Includes the MSH6 Gene

If you and/or other family members had genetic testing of the MLH1 and MSH2 genes responsible for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and a mutation was not found, you may want to consider genetic testing of the MSH6 gene which became available in a number of laboratories in 2005. MSH6 is the third most common gene responsible for HNPCC, also referred to as Lynch syndrome. If you did not have MSH6 testing and are interested in considering it, contact your cancer genetic specialist to discuss in further detail.

8/1/2004 Improved HNPCC and FAP Genetic Testing

Clinical genetic testing of the MLH1 and MSH2 genes responsible for Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also referred to as Lynch syndrome, has been enhanced to detect a greater number of mutations. In addition, clinical genetic testing of the APC gene responsible for Familial Adenomatous Polyposis Colorectal Cancer (FAP) has been enhanced as well. In addition to proofreading or “sequencing” the appropriate gene(s), a different technique, called Southern blotting, is used to detect large mutations that would be missed by sequencing. Other laboratories use different methods to detect mutations and have made enhancements, as well, to their genetic testing for HNPCC and FAP. Please contact your cancer genetic specialist to ask whether there have been improvements to the specific genetic test that you pursued.

10/1/2003 New Genetic Test for Individuals With 20 or More Colorectal Polyps

Individuals with 20 or more colorectal polyps, specifically adenomas, who had genetic testing for Familial Adenomatous Polyposis (FAP) and were not found to carry a mutation in the APC gene may want to consider genetic testing of the MYH gene responsible for MYH-Associated Polyposis (MAP). Studies have shown that approximately 30% of individuals with 15-100 adenomas (who do not have a mutation in the APC gene) have mutations in the MYH gene. In addition, approximately 7% of individuals with greater than 100 adenomas (who do not have a mutation in the APC gene) have mutations in the MYH gene. If you have had 20 or more colorectal adenomas and were not identified to have a mutation in the APC gene, you may want to consider genetic testing of the MYH gene by contacting your cancer genetic specialist.

10/1/2003 Refinement of Tumor Block Test for HNPCC

If you pursued specialized testing on a tumor block from your diagnosis of colorectal cancer and it was identified to have microsatellite instability (MSI) and absent / weak expression of the MLH1 gene yet no mutation was identified in this gene following genetic testing, you may want to consider a new test that looks for hypermethylation of the promoter region that controls expression of the MLH1 gene. If this test identifies hypermethylation, your colorectal tumor was most likely not due to the condition called Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Please contact your cancer genetic specialist to ask whether this testing may be appropriate for you to consider or whether other hereditary cancer syndromes should be considered.

8/12/2002 Improved BRCA1 and BRCA2 Genetic Testing

Genetic testing of the BRCA1 and BRCA2 genes became available on a clinical basis in 1996 and has since been enhanced to include screening for 5 additional large mutations in the BRCA1 gene that would be missed by proofreading or “sequencing” the genes. This additional part of the test is referred to as the 5-site rearrangement panel. Anyone who had BRCA testing prior to this date, in which a mutation was not already identified in the family, may want to consider pursuing the “5-site rearrangement panel” by contacting their cancer genetic specialist. Anyone who had BRCA testing ordered on or after 8/12/02 had the enhanced genetic test which included looking for the 5 additional BRCA1 mutations.

Ongoing Variants of Uncertain Clinical Significance

If you had genetic testing and a variant of uncertain clinical significance was identified, you may want to contact your cancer genetic specialist to learn whether the specific variant has been reclassified as either a mutation that poses an increased risk for various cancers or as a normal variation that differs from one person to the next and poses little if any risk for cancer. In addition, there may be research-based testing available free of charge to further understand the potential significance if any of the variant.