What's New in Cancer Genetics

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 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. Penn State Health Cancer Genetics Program can be reached by calling 717-531-1631.

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.

March 2012 – Panel Testing now available to explore personal and/or family history of cancer

Multi-gene panel tests enable genetics laboratories to analyze multiple cancer susceptibility genes at the same time in a more cost efficient manner. If you previously pursued genetic testing but did not have a multi-gene panel using next generation sequencing technology, you may want to contact a genetics professional to inquire whether additional testing is warranted.

January 2010 - New Recommendation to screen all colon cancer tumors for Lynch syndrome

The Evaluation of Genomic Application in Practice and Prevention (EGAPP) Working Group has recommended that all individuals with a new diagnosis of colorectal cancer be offered genetic screening for Lynch syndrome.  Ask your healthcare provider if your colon cancer tumor was screened for Lynch syndrome.

October 2009Enhanced Test for Lynch Syndrome Includes the TACSTD1/EPCAM Gene

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 MSH2 gene, yet no mutation was identified in this gene following genetic testing, you may want to consider a new test that looks for deletions in the TACSTD1 (EPCAM) gene, which is upstream or right in front of MSH2. Deletions in the EPCAM gene have been found to silence or turn off the MSH2 gene and in doing so, predisposes to colorectal cancer, and potentially other cancers seen in HNPCC / Lynch syndrome. Likewise, if you pursued direct genetic testing for Lynch syndrome which included testing of the MLH1, MSH2, MSH6 and PMS2 genes only, and a mutation was not found, you may want to consider the TACSTD1/EPCAM test as well. 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.

March 2009 - Women with Triple-Negative Breast Cancer are Candidates for Genetic Testing
In a recent study of a group of patients with triple-negative breast cancer diagnosed before age 40, 11% had a BRCA1 or BRCA2 mutation. These patients had little to no family history of breast or ovarian cancer. It was concluded that women with early-onset, triple-negative breast cancer are candidates for genetic testing, even without a family history of breast or ovarian cancer. Current NCCN guidelines state that any woman diagnosed with a triple negative breast cancer (ER negative, PR negative, and Her-2/Neu negative) at 60 years of age or under are appropriate candidates for BRCA1 and BRCA2 testing, regardless of any additional family history.

July 2008New Genetic Test for HNPCC / Lynch Syndrome Includes the PMS2 Gene

If you and/or other family members had genetic testing of the MLH1, MSH2, and MSH6 genes responsible for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) / Lynch Syndrome and a mutation was not found, you may want to consider genetic testing of the PMS2 gene which became available in a number of laboratories in 2008. PMS2 is the fourth most common gene responsible for HNPCC, also referred to as Lynch syndrome. If you did not have PMS2 testing and are interested in considering it, contact your cancer genetic specialist to discuss in further detail.

October 2006 - Further Refinement of Tumor Block Test for HNPCC / Lynch Syndrome

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 a specific somatic (not heritable) mutation (V600E) in the BRAF gene. If this test identifies the presence of the V600E BRAF mutation, your colorectal tumor was most likely not due to Hereditary Non-Polyposis Colorectal Cancer (HNPCC), now referred to as Lynch syndrome. In addition, you may also want to consider testing to look for methylation of the MLH1 promoter which is a sporadic, rather than a hereditary cause of colorectal cancer.  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.

8/1/2006 - Myriad Enhances 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. Anyone who had BRCA testing prior to August 1, 2006, in which a mutation was not already identified in the family, may want to consider pursuing additional testing by contacting a cancer genetics specialist.

1/1/2005 - New Genetic Test for HNPCC/Lynch Syndrome 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/Lynch Syndrome 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 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 MUTYH gene responsible for MUTYH-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 MUTYH 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 MUTYH 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 MUTYH gene by contacting your cancer genetic specialist.

10/1/2003 - Refinement of Tumor Block Test for HNPCC/Lynch Syndrome

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), now preferably called Lynch syndrome. 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 - Myriad has 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 alone. 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.