Genetic Testing by Cancer Site

Abstract

Approximately 1 in every 4 to 5 women with a diagnosis of ovarian cancer has a hereditary gene mutation that is responsible for the development of her cancer. Identifying women at increased risk of developing ovarian cancer due to a hereditary cancer syndrome can allow for early detection or prevention of not only ovarian cancer, but also other cancers, depending on the causative gene. This review focuses on 3 of the most common hereditary ovarian cancer syndromes, hereditary breast and ovarian cancer syndrome (the BRCA1 and BRCA2 genes), Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), and Peutz-Jeghers syndrome, including key features, genetics, and management of these syndromes. In addition, newly discovered genes (eg, RAD51C and RAD51D) linked to ovarian cancer are discussed.

About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants

“…We did not identify any deleterious RAD51D variant in 171 unrelated individuals from pedigrees with BC cases and The carriers of this missense also presented the pathogenic mutation c.694C>T. 3 Although no clearly stated in the article, the carrier of this missense also presented the pathogenic mutation c.694C>T.…”

“…[11][12][13][14] These works show that RAD51D is an OC predisposition gene, but more studies in familial and sporadic OC series would be of value to further clarify the risks associated to OC and BC. 3 The aim of our study was to determine the prevalence of germline RAD51D mutations in a cohort of Spanish BC and/ or OC families previously found to be negative for BRCA1 and BRCA2 mutations.…”

“…The most important risk factor is having a family history of the disease (reviewed in Ref. 3). Approximately 25% of newly diagnosed cases are due to a hereditary mutation in a single gene: 18% in BRCA1 or BRCA2; 5% in other genes of the FanconiAnemia-BRCA DNA repair pathway, including MRE11, BRIP1, PALB2, RAD51C, CHEK2, NBN, RAD50 and BARD1; 1% in genes of DNA mismatch repair pathways (MLH1, MSH2, MSH6 and PMS2) and less than 1% in other genes such as TP53.…”

Overview of Carcinomas in Adolescents: A Descriptive Study Over Twenty Years

“…Given the rarity of these cancers in this age group, it is probably worth proposing genetic counseling to all adolescents with carcinomas in order to study the familial history of cancer, to look for associated abnormalities, to propose performing targeted tests based on clinical presentation and to bank DNA for future research when there is no obvious targeted test. Pediatric oncologists are not well aware of these targeted tests, consequently, genetic counseling seems to be necessary to determine which test is appropriate for which patient (PTEN and RET in thyroid cancer, VHL and MITF in renal carcinoma, PTCH in basal cell carcinoma, APC in polyposis, colon and liver carcinoma, MMR in colon carcinoma and other carcinomas of the Lynch syndrome of tumor spectrum...) [26][27][28][29]. Since TP53 mutations are associated with an excess risk of carcinomas, systematic screening of TP53 could be proposed but such systematic screening should probably be included in research protocols since childhood and adolescent carcinomas without familial history of cancer or multiple primary tumors are not included in the classic criteria for TP53 testing (except adrenocortical carcinoma or choroid plexus tumor, in which TP53 testing is always recommended irrespective of family history) [30].…”

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

“…About 5-7% of BC and 20-25% of OC are thought to be due to rare variants conferring a hereditary predisposition to cancer [1,2]. The penetrance of these rare variants may be highly variable depending on the gene considered.…”