TY - JOUR
T1 - A case of contralateral breast cancer and skin cancer associated with NBN heterozygous pathogenic variant c.698_701delAACA
AU - Gass, Jennifer
AU - Jackson, Jessica
AU - Macklin, Sarah
AU - Blackburn, Patrick
AU - Hines, Stephanie
AU - Atwal, Paldeep S.
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media Dordrecht.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has a positive family history of cancer, presented with contralateral breast cancer and multiple skin malignancies. Genetic testing revealed a frameshift variant in NBN. This gene encodes the protein, nibrin, which is involved in maintaining genomic stability. Several reports have identified heterozygous NBN frameshift (c.2028delT, c.2097dupT, c.657-661delACAAA) and splice site variants (c.1397+delG) in patients with breast cancer. However, our report is the first to describe a heterozygous c.698_701delAACA NBN variant in a patient with breast cancer. Since NBN is involved in DNA integrity, loss of functional protein due to pathogenic variants significantly increases the risk of various cancers. Given the family and personal history of our patient, in connection with previous reports of NBN pathogenic variants predisposition to cancer, this variant is predicted to be pathogenic and clinically significant.
AB - Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has a positive family history of cancer, presented with contralateral breast cancer and multiple skin malignancies. Genetic testing revealed a frameshift variant in NBN. This gene encodes the protein, nibrin, which is involved in maintaining genomic stability. Several reports have identified heterozygous NBN frameshift (c.2028delT, c.2097dupT, c.657-661delACAAA) and splice site variants (c.1397+delG) in patients with breast cancer. However, our report is the first to describe a heterozygous c.698_701delAACA NBN variant in a patient with breast cancer. Since NBN is involved in DNA integrity, loss of functional protein due to pathogenic variants significantly increases the risk of various cancers. Given the family and personal history of our patient, in connection with previous reports of NBN pathogenic variants predisposition to cancer, this variant is predicted to be pathogenic and clinically significant.
KW - Breast cancer
KW - Melanoma
KW - NBN pathogenic variants
KW - Nibrin
KW - Squamous cell carcinoma
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U2 - 10.1007/s10689-017-9982-0
DO - 10.1007/s10689-017-9982-0
M3 - Article
C2 - 28374160
AN - SCOPUS:85016950297
SN - 1389-9600
VL - 16
SP - 551
EP - 553
JO - Familial Cancer
JF - Familial Cancer
IS - 4
ER -