History Of Hereditary Cancer Research Articles

Handling of Germline Findings in Clinical Comprehensive Cancer Genomic Profiling.

Patients found to have presumed germline pathogenic variants (PGPVs) during comprehensive genomic profiling (CGP) require genetic counseling (GC) referrals. We retrospectively investigated the outcomes of patients with PGPVs. Among 159 patients who underwent CGP, we recommended GC for the 16 patients with PGPVs (3 with [FG group] and 13 without [G Group] a family/personal history of hereditary cancer) as well as for the 8 patients with no PGPVs, but a history (F group); 2 (67%), 5 (38%), and 3 (38%) patients received GC in the FG, G, and F groups, respectively. Germline testing results were positive in 1 and 2 patients of the FG and G groups, respectively. Among the patients recommended for GC, 58% did not receive GC due to lack of interest, poor performance status, or death. CGP contributes to the identification of germline variants in patients without a history of hereditary cancer. However, the proportion of patients who undergo GC should be improved.

Hereditary cancer families’ perceptions about biobanking as a healthy control.

e12556 Background: Biobanks are a promising way to identify links between genetic and environmental factors in relation to disease, particularly cancer. However, there has been skepticism among the general public about the purpose of biospecimen donation. Healthy people are beginning to be approached for participation in biobanking based on NIH initiative to establish national repositories. There is a great need to address public concerns about biospecimen donation. There may be additional and unique concerns among families with a history of hereditary cancer. Methods: Participants were recruited through research networks of families across the US who had received genetic counseling/testing. At-risk individuals (18 and over, no personal cancer diagnosis, first degree family member with cancer, had a test for hereditary cancer) completed a 15-item biobanking statement rating worksheet, selecting from 1 (strongly disagree), 2 (agree), 3 (not sure), 4 (disagree) and 5 (strongly agree). Results: 39 participants (100% white, 92.5% female) completed the worksheet. Most participants (87%) agreed confidentiality with medical information was important. 89% thought genetic research and biobanks were useful even if they only produced scientific knowledge instead of cancer cures. 87% felt the public should be consulted on ethical issues in biospecimen research, and permission should be acquired before conducting research on their samples (74%). 56% were unsure if they were exposing themselves to risk if they donated a specimen, while 46% were concerned that their specimen would be connected to their identity. Participants were uncertain if researchers should explain the use of each biospecimen (36% agreed, 33% unsure, 31% disagreed). 92% felt public education about biobanking would increase biospecimen donation. Conclusions: While participants were supportive of genetic research and biobanks, concerns regarding confidentiality and loss of privacy remain among unaffected carriers. There is a need to enhance existing training for researchers to improve understanding of high genetic risk community members’ perceptions about biobanking.

Early onset sebaceous carcinoma

BackgroundOcular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression.FindingsA detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided.A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues.DiscussionThis study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.