scholarly journals PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

2010 ◽  
Vol 126 (3) ◽  
pp. 825-828 ◽  
Author(s):  
Paolo Peterlongo ◽  
Irene Catucci ◽  
Graziella Pasquini ◽  
Paolo Verderio ◽  
Bernard Peissel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Family History ◽  
Familial Breast Cancer ◽  
Germline Mutations ◽  
History Of

scholarly journals Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Joaira Bakkach ◽  
Mohamed Mansouri ◽  
Touria Derkaoui ◽  
Ali Loudiyi ◽  
ElMostafa El Fahime ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Brca2 Gene ◽  
Germline Mutations ◽  
Genetic Alterations ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
History Of

Abstract Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

Germline mutations in early-onset or hereditary breast cancer from the Middle East.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 20-20 ◽  
Author(s):  
Makia J Marafie ◽  
Rabea Al-Temaimi ◽  
Andre Megarbane ◽  
Fahd Al-Mulla
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Middle East ◽  
Middle Eastern ◽  
Germline Mutations ◽  
Illumina Platform ◽  
Family History Of Cancer ◽  
Middle Eastern Women ◽  
History Of ◽  
History Of Cancer

20 Background: Breast cancer is the most common cancer affecting women of Middle Eastern origin. Epidemiologically, breast cancer in the Middle East clusters in families and usually affects women a decade younger than Western women. This dilemma is compounded by the lack of curated databases and ambitious studies that address the roles genetic or genomic may play in breast cancer. Methods: We have exome sequenced 60 Middle Eastern women with moderate and strong family history of cancer or young women without significant family history of cancer. DNA extracted from peripheral blood of patients and matching normal Middle Eastern women without history of familial or sporadic cancers, were subjected to whole-exome sequencing using the HiSeq 2500 Illumina platform and MLPA to map major breast cancer–activating genetic defects. Results: Several novel BRCA1/2 mutations were identified in the minority of these women. However, other complex mutations in non-BRCA1/2 genes appear to play a more subtle role in breast cancer in the Middle Eastern women. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. Conclusions: BRCA1/2 gene mutations are not a significant cause of heritable cancers in the Middle East. The region may benefit from a well-curated region-specific database accessible to clinicians and scientists where clinical and variants information can be deposited from all over the Middle East.

DNA repair germline pathogenic mutation associations with treatment duration and family history in prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 245-245
Author(s):  
James Vu ◽  
Marcus Marie Moses ◽  
Lahiru Ranasinghe ◽  
Patrick Cotogno ◽  
Charlotte Manogue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Family History ◽  
Treatment Outcomes ◽  
Treatment Duration ◽  
Pathogenic Mutation ◽  
Germline Mutations ◽  
Cancer Type ◽  
History Of

245 Background: Germline mutation testing for metastatic prostate cancer patients creates a potential opportunity to personalize targeted therapies to improve treatment outcomes. The goal of this study was to characterize cancer family history, and evaluate treatment outcomes, in mCRPC patients with DNA repair pathogenic germline alterations. Methods: A retrospective study of metastatic PCa patients at Tulane Cancer Center identified 246 patients undergoing germline testing using panels (30-80 genes) (Color.com or Inviate.com). Clinical annotations included family history, life-extending treatments, and treatment duration. Statistical analyses including chi-square and Wilcoxon Rank Sum. Results: In the 246 patients tested for germline mutations, 27 patients (11.0%) had ≥1 DNA repair germline pathogenic mutation (BRCA2 = 11, BRCA1 = 3, CHEK2 = 5, ATM = 3, NBN = 1, PMS2 = 2, MSH2 = 1, PALB2 = 1) while 219 patients (89.0%) possessed no pathogenic mutation in these genes. Patients with a DNA repair pathogenic mutation were more likely to have > 2 family members affected by cancer, regardless of cancer type or degree of relationship (p = 0.04). In the DNA repair population, 5 pathogenic patients had no family history of cancer (18.5%, n = 5). Patients were more likely to have a germline alteration if they had 1 or more first degree relatives affected with breast cancer (p = 0.00001). Median lines of life-extending treatments to date between the pathogenic and non-pathogenic population were equal at 2. There were no significant differences in treatment duration for abiraterone (p = 0.49), enzalutamide (p = 0.99), docetaxel (p = 0.28), cabazitaxel (p = 0.53), carboplatin+docetaxel (p = 0.41), or radium-223 (p = 0.59) between the two groups. Conclusions: In this study, DNA repair pathogenic germline mutations did not affect treatment durations or lines of therapy but these studies are underpowered. The relationship between a family history of breast cancer and a DNA repair pathogenic mutation has not previously been reported.

Germline mutations in Brazilian pancreatic carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16749-e16749
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Luiz A.Senna Leite ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Carcinoma ◽  
Germline Mutations ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
History Of ◽  
History Of Cancer

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

scholarly journals Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abdul Khalid Siraj ◽  
Tariq Masoodi ◽  
Rong Bu ◽  
Sandeep Kumar Parvathareddy ◽  
Kaleem Iqbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Middle Eastern ◽  
Mutation Screening ◽  
Univariate Analysis ◽  
Positive Family History ◽  
Germline Mutations ◽  
Pathogenic Mutations ◽  
History Of

Abstract Background The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited. Methods We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing. Results Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS. Conclusions TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.

Exploring a possible relationship of germline CDKN2A mutations with breast cancer in a multigene panel cohort.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23218-e23218 ◽  
Author(s):  
Darling J Horcasitas ◽  
Holly LaDuca ◽  
Amal Yussuf ◽  
Ginger Chisholm ◽  
Jonah R Chavez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Family History ◽  
Breast Cancer Diagnosis ◽  
Case Control ◽  
Control Analysis ◽  
Cdkn2a Mutation ◽  
Mutation Carriers ◽  
History Of ◽  
Relationship Of

e23218 Background: Germline mutations in CDKN2A have been known to increase the risk of melanoma and pancreatic cancer compared to the general population. With the advent of multi-gene panels, individuals who may not have melanoma or pancreatic cancer are undergoing CDKN2A analysis. Previous studies in homogenous populations have suggested that breast cancer risks may also be increased in CDKN2A. This study aims to further evaluate a possible relationship of CDKN2A mutations with breast cancer through a series of case-control comparisons. Methods: Clinical histories and molecular results were retrospectively reviewed for patients undergoing CDKN2A analysis as part of two diagnostic pan-cancer panels at a single laboratory to ascertain CDKN2A mutation carriers (n = 104) and patients negative for all genes analyzed (n = 20,280). Patients with a personal and/or family history (1st and 2nd degree relatives) of pancreatic cancer and/or melanoma were excluded from case-control analysis. Results: The majority of CDKN2A mutation carriers (82.6%, n = 86/104) had a personal history of cancer documented on the test requisition form. The most common cancers were breast (n = 38, 52.8%), melanoma (n = 37, 43.0%) and pancreatic (n = 6, 7.1%). The average age of breast cancer diagnosis in this cohort was 49.3 years (range 25-84). Family history of breast, melanoma, and/or pancreatic cancer was reported for 54.9%, 46.1%, and 34.3% of CDKN2A mutation carriers, respectively. Females with breast cancer were not more likely to test positive for a CDKN2A mutation than females with cancer other than breast (OR = 0.84, p = 0.79) or unaffected females (OR = 1.02, p = 1). Conclusions: Although CDKN2A mutations were not significantly associated with breast cancer in this cohort, these findings do not necessarily rule out an association of CDKN2A mutations with breast cancer, particularly if risks are moderate or if genotype-phenotype correlations exist. Additional studies involving breast cancer cases unselected for age and family history and/or longitudinal studies of CDKN2A carriers are needed to better understand the relationship between CDKN2A and breast cancer risk.

scholarly journals Impact of Changing Guidelines on Genetic Testing and Surveillance Recommendations in a Contemporary Cohort of Breast Cancer Survivors with Family History of Pancreatic Cancer

2021 ◽  
Author(s):  
Annie Wang ◽  
Jessica N. Everett ◽  
Jennifer Chun ◽  
Cindy Cen ◽  
Diane M. Simeone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Cancer Survivors ◽  
Breast Cancer Survivors ◽  
Degree Relative ◽  
Genetic Risk Assessment ◽  
Changing Practice ◽  
History Of

Abstract Background: Changing practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Methods: Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010-2018 in the NYU Langone Health Breast Cancer Database. Results: Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p<0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Conclusions: Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.

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