PALLD

The PALLD gene, also known as Palladin, codes for a cytoskeletal associated protein

NAME OF SYNDROME(S):
PALLD pathogenic variants (mutations) may confer susceptibility to pancreatic cancer. 

SUMMARY OF SYNDROME:

Pancreatic cancer refers to malignancies of the pancreas, an organ that is approximately six inches long located in the abdomen behind the stomach. The pancreas provides the body with digestive enzymes and certain hormones such as insulin. Most pancreatic cancer begins in the cells that line the ducts of the pancreas. This type of cancer is called pancreatic adenocarcinoma or pancreatic exocrine cancer. 

RISK %S FOR CANCER/DISEASE:

 Unknown, possible higher risk for pancreatic cancer

SUMMARY OF GENE & GENE FUNCTION:

PALLD is located on chromosome 4. The gene encodes the protein palladin, which is involved in forming the cell’s cytoskeleton, or basic structure. As part of the cytoskeleton, PALLD plays an important role in cell shape, interaction with other cells, and flexibility. Some research indicates that PALLD acts as a proto-oncogene, meaning it may also regulate cell growth.

Fun fact: Due to its key role in cell structure, palladin was named in reference to Renaissance architect, Andrea Palladio.

VARIANTS: 

P239S:
While the genetic component in many familial pancreatic cancers remains unknown, a pathogenic variant in PALLD has been identified in some cases. Specifically, Pogue-Geile et al. (2006) described a family of Western European descent (“Family X”) in which individuals with a familial mutation in PALLD developed pancreatic cancer while those without the familial mutation did not. The identified mutation was P239S, a substitution of proline to serine at protein position 239. (This missense mutation occurs in a binding site for alpha-actinin, another key cytoskeletal protein.)

INHERITANCE:

Autosomal dominant, meaning each parent, sibling, and child of an individual with a mutation in PALLD has a 50% chance of also having the mutation.

SCREENING RECOMMENDATIONS:

The impact of current surveillance methods such as endoscopic ultrasound for pancreatic cancer remains uncertain. Early signs of pancreatic cancer may include sudden weight loss, new-onset diabetes, and pain in the upper abdomen. However, pancreatic cancer may also be asymptomatic until the disease advances. 

ADDITIONAL RISK FACTORS:

Risk factors for pancreatic cancer include diabetes, obesity, smoking, heavy alcohol consumption, and some exposure to some toxins such as heavy metals. Therefore, individuals may reduce their risk of pancreatic cancer by maintaining a healthy diet and weight, abstaining from smoking, moderating alcohol intake, and avoiding harmful exposures. 

There are no treatments for pancreatic cancer specific to PALLD mutations at this time.

RESOURCES:

Genetics Home Reference: https://ghr.nlm.nih.gov/gene/PALLD

PanCan, a patient support and advocacy group for pancreatic cancer: https://www.pancan.org

REFERENCES:

National Comprehensive Cancer Network. (2019). Pancreatic Adenocarcinoma (version 3.2019). Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf

Online Mendelian Inheritance in Man. (2019). PALLADIN, CYTOSKELETAL-ASSOCIATED PROTEIN; PALLD. Retrieved from https://omim.org/entry/608092#0001


Pogue-Geile K.L., Chen R., Bronner M.P., Crnogorac-Jurcevic T., Moyes K.W., Dowen S., Otey C.A., Crispin D.A., George R.D., Whitcomb D.C., Brentnall T.A. Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med. 3:2216-2228(2006)


Zogopoulous G., Rothenmund H., Eppel A., Ash C., Akbari M.R., Hedley D., Narod S.A., Gallinger S. The P239S palladin variant does not account for a significant fraction of hereditary or early onset pancreas cancer. Hum. Genet. 121:635-637(2007)