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

Cancer Resource Foundation funding program for cancer genetic testing

The Cancer Resource Foundation (CRF) recently expanded their co-pay assistance program for individuals with limited coverage for cancer genetic testing to a national level. If you meet certain criteria, the CRF will fund up to $520 of your genetic testing. To learn more about this program, please visit http://www.cancer1source.org or contact the cancer genetic counseling program.

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 – New diagnostic testing available for breast, colon and other hereditary cancer syndromes using next-gen sequencing technology

Recently, new genetic testing has become available that provides simultaneous analysis of multiple genes that contribute to an increased risk for various types of cancer. Ambry Genetics has released four next-gen sequencing panels including BreastNext, OvaNext, ColoNext and CancerNext. Each panel focuses on a targeted group of genes that are related to the cancer type depicted by the panel name. For example, BreastNext examines breast cancer susceptibility genes whereas ColoNext examines genes that contribute to an increased risk for colon cancer. Please note that the BreastNext panel is primarily for patients who have previously tested negative for BRCA1 and BRCA2 mutations. If you are interested in learning more about this testing, please contact your cancer genetic specialist to discuss in further detail.

4/7/2011 2011 NCCN Guidelines for Testing of the BRCA1/2 Genes (Hereditary Breast and Ovarian Cancer Syndrome)

The National Comprehensive Cancer Network (NCCN) has updated their testing criteria to help identify families with Hereditary Breast and Ovarian Cancer Syndrome. While meeting 1 or more of these criteria may indicate that there is sufficient family history to warrant consideration of genetic testing of the BRCA1 and BRCA2 genes, it does not guarantee that insurance will cover the genetic testing. Further questions should be directed to a genetics professional.

- Individual from a family with a known deleterious BRCA1/BRCA2 mutation

-Personal history of breast cancer and one or more of the following:
*Diagnosed at less than or equal to 45 years of age
*Diagnosed at less than or equal to 50 years of age with at least 1 close blood relative with breast cancer at less than or equal to 50 years of age and/or at least 1 close blood relative with ovarian/fallopian tube/primary peritoneal cancer at any age
*Two breast primaries when first breast cancer diagnosis occurred prior to age 50
*Diagnosed at less than 60 years of age with a triple negative breast cancer
*Diagnosed at less than 50 years of age with a limited family history (Ex: fewer than 2 first or second degree female relatives or female relatives surviving beyond 45 years)
*Diagnosed at any age with at least 2 close blood relatives with breast and /or epithelial ovarian/fallopian tube/peritoneal cancer at any age
*Close male blood relative with breast cancer at any age
*Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer
*For an individual of ethnicity associated with higher mutation frequency (Ex: Ashkenazi Jewish), no additional family history may be required

-Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer

-Personal history of male breast cancer

- Personal history of breast and/or ovarian cancer at any age with at least 2 or more close blood relatives with pancreatic cancer at any age

-Personal history of pancreatic cancer at any age with at least 2 close blood relatives with breast and/or ovarian and/or pancreatic cancer at any age

-Family history only:
*First or second degree blood relative meeting any of the above criteria
*Third degree blood relative with breast cancer and/or ovarian/fallopian tube/primary peritoneal cancer with at least 2 close blood relatives with breast cancer (at least one less than 50y) and or ovarian cancer

**Close blood relative is defined as first, second or third degree relatives.

December 2010- Testing Available for PALB2, a Pancreatic Cancer Susceptibility Gene
The gene, PALB2, interacts with the BRCA2 gene to repair damaged DNA and maintain the rate of cell growth and division. A mutation in PALB2 may increase one's risk for both pancreatic cancer, as well as breast cancer. If you have a personal and/or family history of pancreatic cancer that is not due to a BRCA2 mutation, especially if there is also a history of breast cancer, you may want to consider genetic testing of the PALB2 gene. If interested, please contact your cancer genetic specialist to discuss in further detail.

July 2010- New Test for KRAS-Variant Which May Increase Ovarian Cancer Risk
The PreOvar test looks for a change or variant in the KRAS gene which was reported in one study to increase risk for ovarian cancer, especially when there is also a family history of ovarian cancer. This variant is reported to be present in 10-11% of the general population, and in 25% of women with epithelial ovarian cancer. Although this test is clinically available through Mira Dx, the Society of Gynecologic Oncologists (SGO) does not currently endorse testing of the KRAS variant at this time. Please contact your cancer genetic specialist if interested in discussing further.

March 2010- New Screening Test to Help Determine Whether an Ovarian Mass is Benign or Malignant Prior to Surgery
OVA1 is a new screening test that measures levels of 5 different proteins in the bloodstream, specifically CA-125, transthyretin, apolipoprotein A1, beta 2 microglobulin, and transferring. The purpose of this screening test is to help determine whether an ovarian mass is benign or malignant prior to surgery. It is the first multi-protein ovarian cancer test cleared by the FDA. OVA1 is not a screening test for the general population but should only be used when an ovarian cyst or mass has been found. If you have been identified to have an ovarian cyst or mass, you may want to discuss this new test with your physician.

January 2010- New Recommendation about Colon Cancer Testing
The Evaluation of Genomic Applications 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. This recommendation stands regardless of family history or age at diagnosis. They did not recommend one specific approach to testing over another.

October 2009 - New Pancreatic Cancer Susceptibility Gene Test Available

A pancreatic cancer susceptibility test for the PALB2 gene has recently become available. PALB2 is a tumor suppressor gene that works along with the BRCA2 gene to regulate cell growth and repair within cells. The PALB2 gene is located on chromosome 16. Individuals who carry 1 mutation in the PALB2 gene have an increased risk to develop pancreatic cancer, as well as breast cancer. In contrast, individuals who carry 2 mutations in the PALB2 gene have a rare, bone marrow failure disorder called Fanconi Anemia. Mutations or changes in the PALB2 gene, resulting in an increased susceptibility for pancreatic and breast cancer, are inherited in a autosomal dominant manor, with a 1 in 2 or 50% risk to one's offspring. Testing is currently being carried out by several laboratories; however, not all insurance companies currently reimburse for the testing. If you have a family or personal history of multiple individuals with pancreatic cancer, please consult with a genetics professional regarding the appropriateness of this new test.

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.

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 or other Lynch associated 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 the condition called Hereditary Non-Polyposis Colorectal Cancer (HNPCC) which is also 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.

12/29/2006 - Updates and Modifications made to Cancer Genetics Program and Website

Penn State Hershey Cancer Institute is proud to announce updates and modifications to the Penn State Hershey 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 $700.

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/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, 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/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).  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.