Genetic Counseling for TP53 Germline Mutations

2012 ◽  
pp. 327-343
Author(s):  
Maria Isabel Waddington Achatz ◽  
Patricia Ashton-Prolla
Keyword(s):  
Genetic Counseling ◽  
Germline Mutations ◽  
Tp53 Germline Mutations

TP53 germline mutations in Portugal and genetic modifiers of age at cancer onset

2009 ◽  
Vol 8 (4) ◽  
pp. 383-390 ◽  
Author(s):  
Carla Pinto ◽  
Isabel Veiga ◽  
Manuela Pinheiro ◽  
Ana Peixoto ◽  
Armando Pinto ◽  
...  
Keyword(s):  
Germline Mutations ◽  
Genetic Modifiers ◽  
Tp53 Germline Mutations

Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer

2019 ◽  
Vol 146 (2) ◽  
pp. 487-495 ◽  
Author(s):  
Shuyan Sheng ◽  
Ye Xu ◽  
Yonghai Guo ◽  
Lu Yao ◽  
Li Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chinese Women ◽  
Germline Mutations ◽  
Clinical Impact ◽  
Tp53 Germline Mutations

scholarly journals Two TP53 germline mutations in a classical Li-Fraumeni syndrome family

2007 ◽  
Vol 6 (3) ◽  
pp. 311-316 ◽  
Author(s):  
Liselotte P. van Hest ◽  
Mariëlle W. G. Ruijs ◽  
Anja Wagner ◽  
Conny A. van der Meer ◽  
Senno Verhoef ◽  
...  
Keyword(s):  
Germline Mutations ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
Tp53 Germline Mutations

TP53 germline mutations in young females with early onset breast cancer in a Mexican population.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e13027-e13027
Author(s):  
Lenny Nadia Gallardo ◽  
Teresa Tusie-Luna ◽  
Maria Isabel Tusie-Luna ◽  
José Díaz-Chávez ◽  
Enrique Macario Herrera Medina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Germline Mutations ◽  
Mexican Population ◽  
Early Onset Breast Cancer ◽  
Young Females ◽  
Tp53 Germline Mutations

Genetic counseling processes and outcomes among prostate cancer patients (ProGen).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS343-TPS343 ◽  
Author(s):  
Donna Rachel Vatnick ◽  
Sandjida Aktar ◽  
Jill E. Stopfer ◽  
Lindsay Kipnis ◽  
Samantha K. Culver ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Mismatch Repair ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

TPS343 Background: Prostate cancer (PC) is among the leading causes of cancer mortality in males. Recent studies found 8-12% of advanced PC cases may be hereditary. Germline mutations have been reported in BRCA1/2, other DNA repair genes including ATM, CHEK2, PALB2 and DNA mismatch repair genes. Genetic testing can inform treatment decisions including drug targeting, such as PARP inhibitors for men with BRCA mutations, and checkpoint inhibitors for those with pathogenic mutations in mismatch repair genes2. Discovering a pathogenic mutation associated with increased cancer risk also prompts dissemination of this information to family, where subsequent testing can lead to risk stratification and impactful opportunities for cancer screening and prevention. It is critical that men with high risk and potentially lethal prostate cancer routinely be offered genetic testing as a component of their cancer care. Genetic counseling services are limited, and more efficient services are needed. Methods: We are investigating video education prior to genetic testing compared with in-person pretest counseling with a licensed genetic counselor (GC). ProGen is an ongoing randomized trial evaluating two distinct models of cancer genetics service delivery in 450 PC cases over a two-year period. The study is conducted in collaboration with Ambry Genetics utilizing a 67-gene cancer panel. The primary aim is analysis of the proportion and type of germline mutations identified. Secondary aims include testing uptake by arm, evaluation of distress, knowledge, satisfaction with testing services, family communication, and impact on cancer care. Results are communicated by telephone with a GC. Inclusion criteria are: potentially lethal PC (metastatic, localized with Gleason score ≥8, rising/persistent PSA after local therapy), early diagnosis (≤ 55 years), prior malignancy, and/or family history potentially indicating a hereditary cancer risk. Enrollment is 74% completed at a single institution. (NCT03328091). 1 Pritchard CC, et al. Inherited DNA‐repair gene mutations in men with metastatic prostate cancer. NEJM. 2016;375:443 2 Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. NEJM . 2015;373(18):1697-1708 Clinical trial information: NCT03328091.

Simultaneous Occurrence of Germline Mutations of SDHB and TP53 in a Patient with Metastatic Pheochromocytoma

2019 ◽  
Vol 105 (4) ◽  
pp. 991-995
Author(s):  
Ewa Gniado ◽  
Colin P Carracher ◽  
Sona Sharma
Keyword(s):  
Antihypertensive Agents ◽  
Pulmonary Nodules ◽  
Germline Mutations ◽  
Simultaneous Occurrence ◽  
Channel Blockers ◽  
Progression Of Disease ◽  
Plasma Metanephrines ◽  
The Right ◽  
Aggressive Clinical Course ◽  
Tp53 Germline Mutations

Abstract Context We describe a patient with metastatic malignant pheochromocytoma who was found to have germline SDHB and TP53 mutations occurring together. Case Description A 39-year-old male presented with neck pain. Magnetic resonance imaging of the neck revealed a C3 vertebral body collapse and an underlying C3 lesion. Computed tomography (CT) of the thorax, abdomen, and pelvis showed multiple skeletal lesions, a sternal mass, bilateral pulmonary nodules, bilateral adrenal masses, and an aortocaval lymph node conglomerate. He underwent biopsy of the sternal mass, which revealed metastatic pheochromocytoma and subsequent blood work showed serum epinephrine levels of 200 pg/mL (normal 10–200 pg/mL), norepinephrine 28 241 pg/mL (normal 80–520 pg/mL), and dopamine 250 pg/mL (normal 0–20 pg/mL). Genetic testing revealed both SDHB and TP53 germline mutations. He was started on α- and β-blockers and calcium channel blockers to control hypertension and tachycardia. Two months after the diagnosis, a CT of the abdomen and pelvis showed progression of disease, with enlargement of the right adrenal mass as well as the aortocaval conglomeration. His plasma metanephrines were significantly elevated. He was started on systemic chemotherapy with cyclophosphamide, dacarbazine, and vincristine. He required several antihypertensive agents, including metyrosine, to control his blood pressure in preparation for chemotherapy. Conclusion This is the first reported case of simultaneous SDHB and TP53 germline mutations occurring in an individual with a highly aggressive clinical course of pheochromocytoma. We speculate that the simultaneous occurrence of these 2 oncogenic mutations may have led to an aggressive tumor progression.

Improving the referral rate of universal genetic counseling for pancreatic ductal adenocarcinoma (PDAC) at the Cleveland Clinic Taussig Cancer Center: A quality improvement project.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 196-196
Author(s):  
Kanika G. Nair ◽  
Brandie Leach ◽  
Selina Sledge ◽  
Megan Kilbane ◽  
Jennifer Bates ◽  
...  
Keyword(s):  
Quality Improvement ◽  
Genetic Counseling ◽  
Patient Education ◽  
Germline Mutations ◽  
Referral Rate ◽  
Quality Improvement Project ◽  
Tumor Board ◽  
Improvement Project ◽  
Referral Rates ◽  
Germline Testing

196 Background: While most PDAC are sporadic, up to 10% are inherited. In 2018, ASCO and NCCN guidelines were updated to recommend that all patients with PDAC be considered for genetic counseling (GC) and germline testing. Furthermore, interest in treating patients with targeted therapy, such as olaparib, for germline mutations is increasing. We implemented a quality improvement project to identify the referral rate to GC for patients with PDAC, with the goal of improving the referral rate to 60%. Methods: Barriers to GC referral were identified using quality improvement tools developed at the ASCO Quality Training Program. Three “plan, do, study, act” (PDSA) cycles were implemented: 1) updating the electronic order and tumor board template to include GC recommendation (Aug–Oct 2019), 2) physician education (Nov–Dec 2019) and 3) patient education and physician reinforcement (Jan–Feb 2020). Baseline data to evaluate impact of PDSA intervention (from April to June 2019) on documented discussions about GC and placement of the referral order was completed via chart review. Results: Between April 2019 to January 2020, 199 patients with PDAC were seen in medical oncology clinic as new patient visits. Thirteen patients had previously completed GC. For the remainder, baseline discussion and referral rates were 25% and 9%, respectively. Discussion and referral rates improved to 55% and 30% after PDSA 1, to 73% and 33% after PDSA 2, and to 95% and 58% after PDSA 3, respectively. Forty-nine patients were referred at the first visit and 23 were referred at a subsequent visit. Forty-six patients underwent GC. In patients who completed germline testing 8.9% (4/45) were found to have a pathogenic variant in BRCA2, TP53, ATM, and MUTYH. Conclusions: With increased physician and patient education, we were able to improve the GC discussion rate from 25% to 95% and referral rate from 9% to 58%. While we did not meet our aim of 60% GC referral rate, we identified obstacles and outlined an improved process for early GC referrals. Enacting processes to reinforce GC referrals for patients with PDAC is likely to increase detection of germline mutations in this population.

Germline mutations in MSH2 and ATM gene in patients with GIST (gastrointestinal stromal tumor) and second epitelial tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23520-e23520
Author(s):  
Silvia Gasperoni ◽  
Laura Papi ◽  
Francesca Castiglione ◽  
Francesca Gensini ◽  
Roberta Sestini ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Lynch Syndrome ◽  
Colon Adenocarcinoma ◽  
Germline Mutations ◽  
Genetic Alterations ◽  
Second Primary ◽  
Sequencing Analysis ◽  
Msh2 Gene ◽  
Primary Tumors ◽  
Therapeutic Implications

e23520 Background: In adult GISTs are frequently sporadic, while rarely GISTs are linked to Carney Triad and Carney-Stratakis Syndrome and NF1. GISTs with second primary tumors are reported in 4-33% of patients in literature and genetic counseling is suggested to explore an underlying germline mutations pathway. Methods: In our Academic Hospital Centre (EURACAN member) in Florence, Italy, we are following patients with GIST and multiple primary tumors with genetic counseling (72 GISTs with second tumors/185 patients with GIST) and germline analysis of the following genetic panel is performed as clinically indicated: BRCA1, BRCA2, MUTYH, MLH1, MSH2, MSH6, CDH1, ATM, TP53, PTEN, CHECK2, PALB2, BARD1, BRIP1, BLM, RAD51C, RAD51D, XRCC2, PMS2, MRE11A, RAD50, NBN, FAM175A, EPKAM, TSK1, MEN1 by sequencing analysis with Illumina MiSeq by kit multiplicom BRCA Hereditary cancer Mastr plus, and bioinformatic analysis by software SOPHIADDM (Sophia genetics) for point genetic alterations of BRCA1 NM_007294.3, BRCA2 NM_000059.3, MUTYH NM_000249, MSH2 NM_000251, MSH6 NM_000179, CDH1 NM_00444360, ATM NM_000051, TP53 NM_000546, PTEN NM_000314, CHEK2 NM_001005735, PALB2 NM_024675, BARD1 NM_000465, BRIP1 NM_032043, BLM NM_000057, RAD51C NM_002876, RAD51D NM_001142571, XRCC2 NM_005431, PMS2 NM_000535, MRE11A NM_005590, RAD50 NM_006732, NBN NM_002485, FAM175A NM_139076, EPCAM NM_002354, STK1 NM_000455, MEN1 NM_000244 and MLPA (Multiplex Ligation-dependent Probe Amplification) test analysis for patients with kit P087-BRCA1,P045-BRCA2(CHEK2, P248-MLH1-MSH2, P003-MLH1/MSH2, P072-MSH6-MUTYH (MRC-Holland). Results: In 3 patients germline mutations have been observed: 1 patient showed the c.1192dupG, p.(Ala398Glyfs*19) pathogenic mutation in exon 7 of MSH2 gene, confirmed by Sanger Sequencing, 1 patient showed c.565-?_1130+?del mutation consisting in heterozygous 3-4-5-6 exons deletion of MSH2 gene, confirmed by MLPA analysis, and in 1 patient the following ATM alteration has been identified in heterozygosis: ATM c.5319+2T > C, p.(?). In the 2 patients with Lynch syndrome with colon adenocarcinoma (MSI-H), synchronous GISTs (1 patient quadruple WT and 1 patient kit ex 11 mutated ) were diagnosed; in the patient with ATM mutation, the diagnosis of GIST (kit ex 11 mutated) occurred after prostate adenocarcinoma and before colon adenocarcinoma (MSI-H). Conclusions: Our analysis suggests that GIST diagnosis could be tumor-related to multiple hereditary tumor syndromes as Lynch Syndrome and Ataxia-Teleangectasia syndrome, the latter being linked in eterozygosis to tumor susceptibility to breast in female. This report represents a high value in terms of genetic counseling for relatives and in terms of therapeutic implications for the patients.

Sign in / Sign up

Export Citation Format

Share Document