Germline variants discovered in lymphoma patients undergoing tumor profiling: a case series.
Ontology highlight
ABSTRACT:
SUBMITTER: Scott AJ
PROVIDER: S-EPMC7719097 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Genomic profiling of colorectal cancer aims to identify actionable somatic mutations but can also discover incidental germline findings. OBJECTIVE:The purpose of this study was to report the detection of pathogenic germline variants that confer heritable cancer predisposition. DESIGN:This was a retrospective study. SETTINGS:The study was conducted at a tertiary-referral institution. PATIENTS:Between 2012 and 2015, 1000 patients with advanced cancer underwent targeted exome sequencing of a 202-gene panel. The subgroup of 151 patients with advanced colorectal cancer who underwent matched tumor-normal (blood) sequencing formed our study cohort. INTERVENTIONS:Germline variants in 46 genes associated with hereditary cancer predisposition were classified according to a defined algorithm based on in silico predictions of pathogenicity. Patients with presumed pathogenic variants were examined for type of mutation, as well as clinical, pedigree, and clinical genetic testing data. MAIN OUTCOME MEASURES:We measured detection of pathogenic germline variants. RESULTS:A total of 1910 distinct germline variants were observed in 151 patients. After filtering, 15 pathogenic germline variants (9.9%) were found in 15 patients, arising from 9 genes of varying penetrance for colorectal cancer (APC (n = 2; 13%), ATM (n = 1; 6%), BRCA1 (n = 2; 13%), CDH1 (n = 2; 13%), CHEK2 (n = 4; 27%), MSH2 (n = 1; 7%), MSH6 (n = 1; 7%), NF2 (n = 1; 7%), and TP53 (n = 1; 7%)). Patients with pathogenic variants were diagnosed at a younger age than those without (median, 45 vs 52 y; p = 0.03). Of the 15 patients, 7 patients (46.7%) with variants in low/moderate- penetrant genes for colorectal cancer would likely have not been tested based on clinical and pedigree criteria, where 2 harbored clinically actionable variants (CDH1 and NF2, 28.5% of 7). LIMITATIONS:This study was limited by its small sample size and advanced-stage patients. CONCLUSIONS:Tumor-normal sequencing can incidentally discover clinically unsuspected germline variants that confer cancer predisposition in 9.9% of patients with advanced colorectal cancer. Precision medicine should integrate clinical cancer genetics to inform and interpret the actionability of germline variants and to provide follow-up care to mutation carriers. See Video Abstract at http://links.lww.com/DCR/A906.
| S-EPMC6415928 | biostudies-literature
Project description:Background: Disturbances in bodily wellbeing represent a key source of psychosocial suffering and impairment related to cancer. Therefore, interventions to improve bodily wellbeing in post-treatment cancer patients are of paramount importance. Notably, body psychotherapy (BPT) has been shown to improve bodily wellbeing in subjects suffering from a variety of mental disorders. However, how post-treatment cancer patients perceive and subjectively react to group BPT aiming at improving bodily disturbances has, to the best of our knowledge, not yet been described. Methods: We report on six patients undergoing outpatient group BPT that followed oncological treatment for malignant neoplasms. The BPT consisted of six sessions based on a scientific embodiment approach, integrating body-oriented techniques to improve patients' awareness, perception, acceptance, and expression regarding their body. Results: The BPT was well accepted by all patients. Despite having undergone different types of oncological treatment for different cancer types and locations, all subjects reported having appreciated BPT and improved how they perceived their bodies. However, individual descriptions of improvements showed substantial heterogeneity across subjects. Notably, most patients indicated that sensations, perceptions, and other mental activities related to their own body intensified when proceeding through the group BPT sessions. Conclusion: The findings from this case series encourage and inform future studies examining whether group BPT is efficacious in post-treatment cancer patients and investigating the related mechanisms of action. The observed heterogeneity in individual descriptions of perceived treatment effects point to the need for selecting comprehensive indicators of changes in disturbances of bodily wellbeing as the primary patient-reported outcome in future clinical trials. While increases in mental activities related to their own body are commonly interpreted as important mechanisms of therapeutic action in BPT, follow-up assessments are needed to evaluate intended and unintended consequences of these changes in cancer patients.
| S-EPMC5635441 | biostudies-literature
Project description:BackgroundThe genomic characterization of sporadically arising gliomas has delineated molecularly and clinically distinct subclasses of disease. However, less is known about the molecular nature of gliomas that are familial in origin. We performed molecular subtyping of 163 tumor specimens from individuals with a family history of glioma and integrated germline and somatic genomic data to characterize the pathogenesis of 20 tumors in additional detail.MethodsImmunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tumor sections to determine molecular subtypes of glioma. For 20 cases, tumor DNA was exome sequenced on an Illumina HiSeq 2000 platform and copy number profiling was performed on the Illumina HumanOmniExpress BeadChip. Genotypes at glioma risk polymorphisms were determined from germline DNA profiled on the Illumina Infinium OncoArray and deleterious germline mutations were identified from germline sequencing data.ResultsAll 3 molecular subtypes of sporadic glioma were represented in the overall case series, including molecular glioblastoma (n = 102), oligodendroglioma (n = 21), and astrocytoma (n = 20). Detailed profiling of 20 of these cases showed characteristic subtype-specific alterations at frequencies comparable to sporadic glioma cases. All 20 cases had alterations in genes regulating telomere length. Frequencies of common glioma risk alleles were similar to those among sporadic cases, and correlations between risk alleles and same-gene somatic mutations were not observed.ConclusionsThis study illustrates that the molecular characteristics of familial tumors profiled largely recapitulate what is known about sporadic glioma and that both germline and somatic molecular features target common core pathways involved in gliomagenesis.Key points1. Familial and sporadic gliomas display highly comparable molecular landscapes. 2. Germline and somatic molecular events target common core pathways involved in gliomagenesis. 3. Carriage of germline glioma risk variants is not associated with somatic events in the same gene.
| S-EPMC6231201 | biostudies-literature
Project description:IntroductionIntradural extramedullary (IDEM) spinal cord tumors account two thirds of all intraspinal tumors. These tumors produce pain syndromes, a variety of neurological symptoms-motor, sensory, sphincter or a combination of thereof. Preferred treatment is microsurgical radical resection. The objective of this study was analyzed and discuss about functional outcome in IDEM.Presentation of caseWe present serial case of 15 patients, that consist of 8 males and 7 females, with the mean age of 43,4 years old, ranging from 16 to 82 years old. The outcomes were followed up with Karnofsky Score and Tomita to analyzed metastasis of the tumor. The mean of Karnofsky score in this study was 74 with no patient had metastatic intradural tumor, therefore the Tomita score in these patients is incalculable.DiscussionMRI confirmed the location and extent of the tumor for definitive diagnosis. We then performed excision of the tumor or decompression of the spinal canal followed by posterior stabilization if needed. Minimal complaint regarding pain and/or numbness were found. Post operation functional outcome of the patient is monitored using Karnofsky score.ConclusionIn all except one patient, the functional outcome of the patients is greater than 50 based on Karnofsky score. In this case series, the good functional outcome is due to all tumor were primary tumor which originate from the spine. Furthermore, all tumor had benign characteristic based on the anatomical pathology result. In consequence, gross total resection can be achieved thus resulting a good overall functional outcome of the patients.
| S-EPMC7201154 | biostudies-literature
Project description:IntroductionSurgery can be an effective treatment for epilepsy if the seizure onset is adequately localized. Invasive monitoring is used if noninvasive methods are inconclusive. Initial invasive monitoring may fail if the pre-surgical hypothesis regarding location of epileptic foci is wrong. At this point, a decision must be made whether to remove all electrodes without a clearly defined location of onset or to implant additional electrodes with the aim of achieving localization by expanding coverage.MethodsElectrodes were placed according to a hypothesis derived from noninvasive monitoring techniques in adult patients with long term epilepsy. Seizure onset was not clearly localized at the end of the invasive monitoring period in ten patients, and additional electrodes were placed based on a new hypothesis that incorporated data from the invasive monitoring period.ResultsSuccessful localization was achieved in nine patients. There were no complications with adding additional electrodes. At final follow up, four patients were seizure free while four others had at least a 50% reduction in seizures after undergoing surgical intervention.ConclusionSeizure foci were localized safely in 90% of adult patients with long term epilepsy after implanting additional electrodes and expanding coverage. Patients undergoing invasive monitoring without clear localization should have additional electrodes placed to expand monitoring coverage as it is safe and effective.
| S-EPMC9284396 | biostudies-literature
Project description:Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well.To estimate the burden of germline variants identified through routine clinical tumor sequencing.Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014.The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors.The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99.9%; 95% CI, 99.6%-99.9%).Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations.
| S-EPMC5477989 | biostudies-other
Project description:Primary pulmonary Hodgkin lymphoma (PPHL) is very rare and typically involves the superior portion of the lung. Pulmonary involvement is observed in 15-40% of Hodgkin lymphoma patients. Three such patients who presented with an unusual form of PPHL in radiological studies, i.e., multiloculated cavitary lesions, were admitted to our hospital. These lesions represent a new pathological and radiological feature of PPHL.
| S-EPMC5869374 | biostudies-other
Project description:BackgroundLimited data exist on strain changes after transcatheter aortic valve implantation (TAVI) in patients with aortic regurgitation (AR).Case summaryThree patients with AR undergoing TAVI showed an initial reduction in global longitudinal strain (GLS), followed by sustained GLS improvement within the first year.DiscussionFindings align with those of surgically treated patients with AR. There is a possible superiority of GLS to left ventricular end-diastolic diameter ratio in assessing patients with severe volume overload.
| S-EPMC11303856 | biostudies-literature
Project description:Germline variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5-10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n?=?755) cancer patients. Gene signatures derived from the genes containing functionally germline variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n?=?200 and 295, P?=?1.4?×?10-3). Furthermore, we compared our results with the widely known Oncotype DX test (i.e., Oncotype DX breast cancer recurrence score) and outperformed prediction for both high- and low-risk groups. Finally, we found that recurred patients possessed a higher rate of germline variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation, and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients' outcomes in breast cancer.
| S-EPMC6825127 | biostudies-literature
Project description:BACKGROUND:Matched tumor-normal sequencing, applied in precision cancer medicine, can identify unidentified germline Medically Actionable Variants (gMAVS) in cancer predisposition genes. We report patient preferences for the return of additional germline results, and describe various gMAV scenarios delivered through a clinical genetics service. METHODS:Tumor profiling was offered to 1960 advanced cancer patients, of which 1556 underwent tumor-normal sequencing with multigene hotspot panels containing 20 cancer predisposition genes. All patients were provided with an IRB-approved consent for return of additional gMAVs. RESULTS:Of the whole cohort 94% of patients consented to be informed of additional germline results and 5% declined, with no statistically significant differences based on age, sex, race or prior genetic testing. Eight patients were found to have gMAVs in a cancer predisposition gene. Five had previously unidentified gMAVs: three in TP53 (only one fulfilled Chompret's Revised criteria for Li-Fraumeni Syndrome), one in SMARCB1 in the absence of schwannomatosis features and one a TP53 variant at low allele frequency suggesting an acquired event in blood. CONCLUSION:Interest in germline findings is high among patients who undergo tumor profiling. Disclosure of previously unidentified gMAVs present multiple challenges, thus supporting the involvement of a clinical genetics service in all tumor profiling programs.
| S-EPMC6085686 | biostudies-literature