palb2-related cancer

Ambry Genetics was the first lab to offer clinical PALB2 testing; PALB2 testing is currently available as a single gene test and as a component of several multi-gene panels that include PALB2.  In over 5 years of offering PALB2 testing, we have analyzed over 15,000 patients for this gene.

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Ambry Genetics was the first lab to offer clinical PALB2 testing; PALB2 testing is currently available as a single gene test and as a component of several multi-gene panels that include PALB2.  In over 5 years of offering PALB2 testing, we have analyzed over 15,000 patients for this gene.

The gene PALB2 is a tumor suppressor gene that has been identified as a breast and pancreatic cancer susceptibility gene. It interacts with BRCA2 to repair damaged DNA and help maintain the rate of cell growth and division. 

Monoallelic (one copy) mutations in this gene have been associated with cancers also seen in BRCA2 mutation carriers, including breast cancer, while biallelic (two copies) mutations have been associated with Fanconi Anemia Type N (FA-N). PALB2 Genetic Testing may be considered for those with familial pancreatic cancer, those with familial breast cancer who tested negative for BRCA1 and BRCA2 mutations, and for those with a confirmed or suspected clinical diagnosis of Fanconi Anemia who have tested negative for other Fanconi Anemia genes.

Ambry Genetics offers a comprehensive menu of testing options that include PALB2:

Disease Name 
PALB2-Related Cancer
Fanconi Anemia, PALB2-Related
Disease Information 

Individuals with a PALB2 mutation may have an increased risk to develop female breast cancer and pancreatic cancer.  It is also possible that there is an increased risk for male breast cancer, ovarian cancer, and prostate cancer.  Individuals with a PALB2 mutation have a 50% chance of passing the mutation on to their children.  

  • Breast Cancer: PALB2 mutations may be associated with at least a two-fold increase in breast cancer susceptibility.6  A recent article concluded that in the context of a strong family history, mutations in PALB2 may be associated with a 58% risk of breast cancer.  Without a family history, the risk for breast cancer was estimated to be 35% (the difference attributed to genetic and/or environmental modifiers).8
  • Fanconi anemia type N (FA-N): Fanconi anemia is characterized by physical abnormalities including short stature, abnormal skin pigmentation, malformations of the skeletal and central nervous system, developmental delays, and bone marrow failure. Reduction of PALB2 protein activity prevents proper DNA repair which increases the susceptibility for several types of cancer within this disorder.
Testing Benefits & Indication 

PALB2 genetic testing may be considered for those with familial pancreatic cancer, those with familial breast cancer who tested negative for mutations in the BRCA1 and BRCA2 genes, and in those with a confirmed or suspected diagnosis of Fanconi Anemia who have tested negative for other Fanconi anemia genes. Patients who carry a mutation in the PALB2 gene may benefit from increased cancer surveillance and prophylactic treatment assessment for other cancers associated with PALB2. Close relatives of patients with mutations in PALB2 may also benefit from knowing their genetic status for appropriate surveillance and treatment. 

Test Description 

This Ambry Test is a gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-13 of the PALB2 gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specific mutation analysis for individual PALB2 mutations known to be in the family is also available.

Mutation Detection Rate 

Greater than 99.9% of described PALB2 sequence mutations are detected by this test. Sequence mutations account for 90-93% of known PALB2 mutations.  An additional 7-10% of PALB2 mutations may be gross deletions that are not identified by this methodology, but would be identified through duplication/deletion analyses that are included on BreastNext, OvaNext, PancNext, CancerNext, and CancerNext-Expanded.

Specimen Requirements 

Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice.  
Prenatal: Testing for those under 18 years of age: Please call one of our Genetic Counselors to discuss your case.

Billing Codes 
Test Code Technique
2360 PALB2 Gene Sequence Analysis

 

Turnaround Time 
Technique Days
PALB2 Gene Sequence Analysis 14-21

 

Specialty 
Genes 
References 

1. National Institute of Health resources page. National Cancer Institute site. click here. Accessed August 3, 2009.

2. Couglin SS, et al. Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 2000;11:915-923. [PMID: 11142526]

3. Jones A, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009; 324(5924):217. [PMID: 19264984]

4. Xia B, et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2006; 22:719-729. [PMID: 16793542]

5. Reid S, et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007 Feb; 39(2):142-3. [PMID: 17200671]

6. Tischkowitz M et al. Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci USA. 2007 Apr 17; 104(16):6788-93. [PMID: 17420451]

7. Kim DH, et al. Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations. Fam Cancer. 2009; 8(2):153-158. [PMID: 18855126]

8.  Antoniou AC, et al.  Breast-cancer risk in families with mutations in PALB2.  NEJM.  2014; 371(6):497-506. [PMID: 25099575]