PALB2-Related Cancer

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

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

Monoallelic mutations in this gene have been associated with cancers also seen in BRCA2 mutation carriers, including breast cancer, while biallelic 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.

The Ambry Test: PALB2-Related Cancer is a Gene Sequence Analysis that can detect approximately 99% of described PALB2 mutations.

Disease Name 
PALB2-Related Cancer
Breast cancer, Familial
Fanconi Anemia, PALB2-Related
Disease Information 

According to the US National Cancer Institute, more than 40,000 new cases of pancreatic cancer are reported a year with over 35,000 estimated deaths.1 Although the majority of pancreatic cancer is sporadic, certain risk factors including environmental and genetic factors, seem to increase the chances of onset. Studies by the American Cancer Society have concluded that there is a genetic susceptibility to pancreatic cancer, and individuals with a first-degree relative with pancreatic cancer are at an increased risk of developing pancreatic cancer themselves.2 Approximately 5-10% of individuals with pancreatic cancer report having an affected family member.3

PALB2, partner and localizer of BRCA2, is a tumor suppressor gene that has been identified as a pancreatic cancer susceptibility gene.3 PALB2 interacts with BRCA2 to repair damaged DNA and help maintain the rate of cell growth and division. Monoallelic mutations in this gene have been associated with BRCA2-related cancers, including breast cancer, while biallelic mutations have been associated with Fanconi anemia type N (FA-N).4,5

  • Breast Cancer: PALB2 mutations may be associated with a two-fold increase in breast cancer susceptibility.6 These mutations result in an abnormally short PALB2 protein, which is unable to work with BRAC2, another known breast cancer susceptibility gene, in repairing damaged DNA causing an abnormal buildup of damaged cells.
  • 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 

Approximately 99% of described PALB2 mutations are detected by this test.

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]