<i>BRCA</i> mutated pancreatic cancer: A change is coming

Rosen, Michael N.; Goodwin, Rachel; Vickers, Michael M.

doi:10.3748/wjg.v27.i17.1943

Cited by 53 publications

(51 citation statements)

References 82 publications

(125 reference statements)

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“…BRCA1 mutations in FPC have not been reported as well as BRCA2 , but with a lower frequency [ 35 ]. Here, we found a higher percentage of BRCA1 mutations in 10.7% of patients, not in line with data reported (1.2–2.6%) [ 26 , 27 , 36 ]. Moreover, in a retrospective study on FPC families, BRCA1 mutations occur in 9.5% [ 28 ], this could be due to a different ethnic distribution.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Vietri

Goletti

Caliendo

et al. 2022

Genes

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Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer death worldwide; most of cases are sporadic, however about 5% to 10% report a hereditary predisposition. Several hereditary syndromes have been associated with familial pancreatic cancer (FPC) onset, including hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), Familial atypical multiple mole melanoma (FAMMM), Familial adenomatous polyposis (FAP), Li–Fraumeni syndrome (LFS),Peutz–Jeghers syndrome (PJS), and Hereditary pancreatitis (HP).The aim of this study was to determine the mutational status of a cohort of 56 HBOC families, 7 LS families, 3 FAP and FAMMM families, and 1 LFS family with at least one case of PDAC. Mutation analysis of BRCA1/2, ATM, CHEK2, PALB2, RAD51C, RAD51D, NBN, CDH1, TP53, MLH1, MSH2, MSH6, and PMS2genes, showedmutation in BRCA1/2, MLH1, and APC genes. We founda high mutation rate in patients belong HBOC and LS families, with a percentage of 28.6% in both syndromes and prevalence in HBOC of BRCA2 mutations with one case of double mutation in BRCA2 gene. In FAP family, we found a pathogenic mutation in APC gene in 1/3 families. We observed an early onset of PDAC and a lower survival in PDAC patients belonging to mutated families, while no evidence of possible pancreatic cancer cluster regions was found. Moreover, we identified a novel BRCA2 germline mutation, c.5511delT (p.Phe1837LeufsX3), not reported in any database, that segregated with disease in HBOC patients. Mutational analysis was extended to family membersof mutated patients, both healthy and cancer affected, which revealed 23 unaffected family members that inherited the proband’s mutation. Although correlative by its nature, the presence of a BRCA mutation in PDAC patients may have benefits in terms of optimized treatment and longer outcome.

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Section: Discussionsupporting

confidence: 83%

“…Moreover, the mutation rate in HBOC and LS, was higher (28.6%) than data previously found, showing the frequency of mutation in BRCA1/2 genes be up to 17% in HBOC and in MMR genes up to 12% in LS [ 26 ]. The difference in mutation prevalence could be influenced by the selection of the patients included.…”

Section: Discussionmentioning

confidence: 97%

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Vietri

Goletti

Caliendo

et al. 2022

Genes

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“…A prospective study of 5,149 females with BRCA1 or BRCA2 carriers showed a significant 2.4-fold increase in the incidence of pancreatic cancer and the increase in the incidence of pancreatic cancer was similar for BRCA1 (SIR = 2.55) and BRCA2 (SIR = 2.13) [ 85 ]. Among unselected pancreatic cancer patient cohorts, multiple studies have shown to estimate the incidence of germline BRCA mutations ranged from 0.7–5.7% for BRCA2 and 0.3–2.3% for BRCA1 [ 86 ]. Of the 145 Jewish pancreatic adenocarcinoma patients, 8 patients (5.5%) were found to have BRCA mutations, 6 patients (4.1%) carried a BRCA2 mutation (6174delT) and 2 patients (1.3%) carried a BRCA1 mutation (185delAG and 5382insC) [ 87 ].…”

Section: Differences Of Other Brca -Related Cancers Risks By Brca1/2 Mutationmentioning

confidence: 99%

Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Sekiguchi

Nishino

Enomoto

2021

Genes

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Hereditary breast and ovarian cancer is caused by a germline mutation in BRCA1 or BRCA2 genes. The frequency of germline BRCA1/2 gene mutation carriers and the ratio of germline BRCA1 to BRCA2 mutations in BRCA-related cancer patients vary depending on the population. Genotype and phenotype correlations have been reported in BRCA mutant families, however, the correlations are rarely used for individual risk assessment and management. BRCA genetic testing has become a companion diagnostic for PARP inhibitors, and the number of families with germline BRCA mutation identified is growing rapidly. Therefore, it is expected that analysis of the risk of developing cancer will be possible in a large number of BRCA mutant carriers, and there is a possibility that personal and precision medicine for the carriers with specific common founder mutations will be realized. In this review, we investigated the association of ovarian cancer risk and BRCA mutation location, and differences of other BRCA-related cancer risks by BRCA1/2 mutation, and furthermore, we discussed the difference in the prevalence of germline BRCA mutation in ovarian cancer patients. As a result, although there are various discussions, there appear to be differences in ovarian cancer risk by population and BRCA mutation location. If it becomes possible to estimate the risk of developing BRCA-related cancer for each BRCA mutation type, the age at risk-reducing salpingo-oophorectomy can be determined individually. The decision would bring great benefits to young women with germline BRCA mutations.

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“…Besides the analysis of consequences and biotypes, we were interested in evaluating whether clinically relevant and therapeutically meaningful gene variants are properly reflected by ev- and cfDNA analysis in comparison to tumor biopsy samples. To this end, the incidence of germline pathogenic BRCA variants in pancreatic cancer was described with a prevalence ranging from 0.3–2.3% for BRCA1 and 0.7–5.7% for BRCA2 [ 47 ]. BRCA variants that impair protein function are known to sensitize tumors to platinum analogs and inhibition with the poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative Panel Sequencing of DNA Variants in cf-, ev- and tumorDNA for Pancreatic Ductal Adenocarcinoma Patients

Waldenmaier¹,

Schulte²,

Schönfelder³

et al. 2022

Cancers

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Pancreatic ductal adenocarcinomas (PDACs) are tumors with poor prognosis and limited treatment options. Personalized medicine aims at characterizing actionable DNA variants by next-generation sequencing, thereby improving treatment strategies and outcomes. Fine-needle tumor biopsies are currently the gold standard to acquire samples for DNA profiling. However, liquid biopsies have considerable advantages as they are minimally invasive and frequently obtainable and thus may help to monitor tumor evolution over time. However, which liquid analyte works best for this purpose is currently unclear. Our study aims to directly compare tumor-, circulating free (cf-) and extracellular vesicle-derived (ev)DNA by panel sequencing of matching patient material. We evaluated copy number variations (CNVs), single nucleotide variants (SNVs) and insertions and deletions (indels). Our data show that evDNA contains significantly larger DNA fragments up to 5.5 kb, in line with previous observations. Stringent bioinformatic processing revealed a significant advantage of evDNA with respect to cfDNA concerning detection performance for SNVs and a numerical increase for indels. A combination of ev- and cfDNA was clearly superior for SNV detection, as compared to either single analyte, thus potentially improving actionable variant prediction upon further optimization. Finally, calling of CNVs from liquid biopsies still remained challenging and uninformative.

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BRCA mutated pancreatic cancer: A change is coming

Cited by 53 publications

References 82 publications

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation

Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Comparative Panel Sequencing of DNA Variants in cf-, ev- and tumorDNA for Pancreatic Ductal Adenocarcinoma Patients

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