bims-lifras 2022-03-20 papers

Cancer Genet. 2022 Mar 05. pii: S2210-7762(22)00022-9. [Epub ahead of print]264-265 16-22

Somatic tumor testing implications for Lynch syndrome germline genetic testing.

Kathleen Barrus, Natasha Purington, Nicolette Chun, Uri Ladabaum, James M Ford.

Clinicians involved in cancer treatment often utilize somatic tumor sequencing to help tailor chemotherapy and immunotherapy. However, somatic tumor sequencing can also identify patients at risk for germline pathogenic variants causing cancer predisposition syndromes like Lynch syndrome. The extent to which clinicians realize this implication of tumor sequencing is currently unclear. We performed a retrospective chart review of Stanford Health Care patients who had somatic variant(s) in the Lynch syndrome genes or microsatellite instability identified on tumor sequencing to determine the proportion of patients who were referred to genetics. Among 6,556 patients who had tumor testing, 90 (1.37%) had findings compatible with Lynch syndrome. Of the 62 patients who had not already seen genetics, 47/62 (75.8%) were not referred to genetics for germline testing. Additionally, 26/47 (55.3%) of these individuals had a tumor type within the Lynch syndrome spectrum. Of the 10 patients who did elect germline testing after tumor sequencing, 3/10 were positive for Lynch syndrome. Our study highlights the need for specific guidelines to inform clinician referral practices on germline follow-up of somatic tumor testing and demonstrates the importance of continued research on the relationship between somatic tumor variants and germline variants to inform such guidelines.

Keywords: Genetic counseling; HNPCC; Lynch syndrome; Somatic tumor sequencing

DOI: https://doi.org/10.1016/j.cancergen.2022.02.010

Front Genet. 2022 ;13 718689

The First Case Report of a Patient With Oligodendroglioma Harboring CHEK2 Germline Mutation.

Xueen Li, Hao Xue, Ningning Luo, Tiantian Han, Mengmeng Li, Deze Jia.

Introduction:CHEK2 (Checkpoint kinase 2) germline mutations were associated with an elevated risk of breast cancer, colorectal cancer, and other familiar cancers. Loss-of-function variants in CHEK2 are known to be pathogenic. Germline CHEK2 mutations have also been observed in medulloblastoma and primary glioblastomas. Currently, there is no direct evidence supporting the relationship of CHEK2 with central nervous system tumors. Case presentation: A case of an oligodendroglioma patient harboring the germline CHEK2 p.R137* mutation was reported. CHEK2 p.R137* mutation occurred in the forkhead-associated domain. Given the absence of other known genetic predisposing risk factors, we considered that oligodendroglioma might be associated with the CHEK2 mutation. The patient in our case might have a high risk of breast cancer and other multiple primary tumors. Her siblings and offspring would have a 50% chance of having the same variant. Conclusion: We reported a case of an oligodendroglioma patient with a family history of gastrointestinal tumors harboring the germline CHEK2 pathogenic variation. This is the first report of the association between the CHEK2 pathogenic variation and brain tumors that warrants further validation in larger cohorts.

Keywords: CHEK2 gene; CNS tumor; germline mutation; oligodendroglioma; potential genetic predisposition

DOI: https://doi.org/10.3389/fgene.2022.718689

Clin J Oncol Nurs. 2022 Apr 01. 26(2): 147-150

The Genetic Management Clinic: Oncology Nurses and Management of Hereditary Cancer Risk.

Stephanie Hoopes, Virginia Simmons, LeAnn Perkins.

Integrating clinics designed to manage hereditary cancer risk into oncology care models has the potential to improve navigation of individuals predisposed to increased cancer risk through risk-reducing education, as well as recommendations for cancer screening and surveillance. Oncology nurses have the unique opportunity and optimal position to navigate patients through the complex subject of genetics and hereditary cancer syndromes. Effectively and efficiently navigating patients with pathogenic variants to minimize and manage hereditary cancer risk has the potential to improve patient outcomes.

Keywords: Patient education; genetic counseling; genetics; hereditary cancer risk; navigation

DOI: https://doi.org/10.1188/22.CJON.147-150

Fam Cancer. 2022 Mar 16.

Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review.

S H Beck, A M Jelsig, H M Yassin, L J Lindberg, K A W Wadt, J G Karstensen.

Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.

Keywords: Breast cancer; Colorectal cancer; Extraintestinal neoplasms; Intestinal neoplasms; NTHL1 tumor syndrome; NTHL1-associated polyposis

DOI: https://doi.org/10.1007/s10689-022-00291-3