BRIP-1 germline mutation and its role in colon cancer: presentation of two case reports and review of literature

Abstract

Background Hereditary colon cancer is characterized by the inheritance of an abnormal gene mutation which predisposes to malignancy. Recent advances in genomic medicine have identified mutations in “novel” genes as conferring an increased risk of colorectal cancer. Mutations in the BRIP1 gene ( BRCA1 Interacting Protein C- terminal helicase 1) are known to increase the risk of ovarian and breast cancers, but this genes association with colon cancer has not been previously reported. Case presentation We describe two patients with colon cancer whose tumor tissue were found to harbor BRIP1 mutations on analysis by next-generation sequencing. These patients were confirmed by analysis of lymphocytes to carry the mutation in the germline as well. Conclusions These case reports highlight a previously unreported association of BRIP1 germline mutations with colon cancer predisposition.

Novel role of BRCA1 interacting C‐terminal helicase 1 (BRIP1) in breast tumour cell invasion

“…In the present study, we tested the hypothesis that BRIP1 can promote both BC cell growth and metastasis. The results of the present study are summarized as follows: (a) structural validation experiments were consistent with our previous findings, 19 showing fivefold overexpression of BRIP1 in all types of BC tumour samples compared with normal/benign breast tissues; (b) functional validation approaches revealed a novel role of BRIP1 in promoting breast tumour cell growth and progression. In fact, siRNA down‐regulation of BRIP1 attenuated significantly cell proliferation by inducing cell cycle arrest.…”

“…Consistent with these observations, our results showed clearly that both the protein and mRNA levels of BRIP1 were overexpressed in various BC cell lines compared with control normal/immortalized and normal/control breast cells, suggesting that BRIP1 might act as an oncogenic driver in BC. Interestingly, previous study revealed the presence of BRIP1 germline mutations in BC patients without any BRCA mutation, suggesting a link between BRIP1 mutations and BC susceptibility 19 . Collectively, although BRIP1 is considered as a tumour suppressor gene, it is amplified in sporadic cancers, 36 thus supporting our previous 7 and current findings, suggesting that BRIP1 amplification in sporadic cancers could explain the oncogenic role of BRIP1.…”

“…Interestingly, previous study revealed the presence of BRIP1 germline mutations in BC patients without any BRCA mutation, suggesting a link between BRIP1 mutations and BC susceptibility. 19 Collectively, although BRIP1 is considered as a tumour suppressor gene, it is amplified in sporadic cancers, 36 thus supporting our previous 7 and current findings, suggesting that BRIP1 amplification in sporadic cancers could explain the oncogenic role of BRIP1.…”

Population-wide Screening for Germline Variants of Hereditary Cancer Genes in 12K Unselected Japanese Colorectal Cancers and 27K Controls

“…A recent meta-analysis of 14 studies (45) examining CRC risk in BRCA1/2 carriers concluded that BRCA1 mutation carriers had increased CRC risk (OR=1.49), whereas BRCA2 mutation carriers did not (OR =1.09). BRIP1 was reported to be associated with ovarian (30) and breast cancers (31), and one study suggested its association with CRC development in two cases (46). In our study, pathogenic variants of BRIP1 showed a 3.6 OR, which is higher than BRCA1/2, indicating that it is worth being included on a list of panel sequencing to assess cancer risk, and a carrier with pathogenic variants of BRIP1 should be subjected to CRC screening in addition to ovarian and breast cancers.…”

Intracellular hyaluronic acid-binding protein 4 (HABP4): a candidate tumor suppressor in colorectal cancer

“…It is the third most common cancer diagnosed in the United States, with an estimated 104,610 new cases and 43,340 deaths for 2020 [1]. The development of colon cancers has been related to both somatic and germline mutations [2,3]. In an analysis of familial colon cancer risk-associated SNP haplotypes, the human gene encoding the protein…”