BR_PALB2

PALB2 Mutation Panel

PALB2 Overview:

PALB2 is abbreviated as Partner And Localizer of BRCA2[1].
PALB2 goes in hand with the BRCA genes during the process of DNA damage response[1].
PALB2 was initially detected as BRCA2 interacting protein which acts as an important key for BRCA2 genome functions [2&3], which also interacts with BRCA1 [4].
The occurrence of PALB2 mutations is very rare but is considered as an important factor in human breast cancer [5].

PALB2 mutations and Cancer

Mutations in PALB2 may at times lead to a defective DNA repair[1].
PALB2 germline mutations results in losing the genome stability which results in inducing cancer onset and progression through the accumulation of the defects in DNA [6].
Heterogenous nature of PALB2 germline mutation may cause DNA replication and DNA damage response [7].
Though the occurrence of PALB2 mutations are rare, it is roughly estimated that there is an increased risk of this particular mutation when compared to BRCA2 mutations[8].
The biallelic germline mutation and loss of function in PALB2 gene is also known to cause a condition called Fanconi’s anaemia [5].
PALB2 mutations is also associated with the ovarian cancer susceptibility[9].

PALB2 mutation risk factors in breast cancer:

PALB2 is also considered as one of the important causes of hereditary breast cancer[10&11].
Though its occurrence is found to elevate, this gene is denoted as moderate penetrance in breast and ovarian cancer gene compared to other genes[12].
PALB2 mutations must be encouraged in women who have genetically inherited Hereditary Breast and Ovarian Cancer (HBOC) in case of a strong familial history for cancer[12].
The monoallelic loss of functional mutation results in an elevated risk of breast and pancreatic cancer [5].
The risk of PALB2 mutation is twice or thrice higher the women above 55 years of age and four times higher for women above the age group of 84.[13].
In case of cancer occurrence without family history, the risk of breast cancer in women with PALB2 mutation until up to age of 70 is nearly 33%
There is an estimated risk of 58% breast cancer occurrence in women with PALB2 mutation having family history of cancer [14].

Risk of other diseases:

Additional to breast cancer, PALB2 mutation have increased the risk of ovarian, prostrate and pancreatic cancer[5].
PALB2 mutation has a great influence in case of familial inheritance of pancreatic cancer[15].
Apart from the above-mentioned cancer types, PALB2 has an increased possibility in causing melanoma due to an increased in BRCA2 mutation carriers.
Apart from cancer, mutation in this gene also causes Fanconi’s anaemia (FA) as PALB2 is one of the two important genes causing FA.
PALB2 along with BRCA2 also show an elevated risk to childhood solid tumor with bi-allelic mutation carrier[15, 16 and 17].
PALB2 mutations may also rise in BRCA1/2 negative patients those have BRCA2 like cancer phenotype (i.e.,) BRCA2 associated tumors.

Reference: