paywalled: Dosage Effect of BRCA1 and BRCA 2 Mutated Allelic Transcript (French Canadian)

Dosage Effect of BRCA1/2-Mutated Allelic Transcript:

We hypothesized that the transcriptome of primary cultures of morphologically normal ovarian surface epithelial cells could be altered by the presence of a heterozygous BRCA1 or BRCA2 mutation.

We aimed to discover early events associated with ovarian carcinogenesis, which could represent putative targets for preventive strategies of this silent killer tumor. We identified the first molecular signature associated with French Canadian BRCA1 or BRCA2 founder mutations in morphologically normal ovarian epithelial cells. We discovered that wild-type and mutated BRCA2 allelic transcripts were expressed not only in morphologically normal but also in tumor cells from BRCA2-8765delAG carriers. Further analysis of morphologically normal ovarian and tumor cells from BRCA1-4446C>T carriers lead to the same observation.

Our data support the idea that one single hit in BRCA1 or BRCA2 is sufficient to alter the transcriptome of phenotypically normal ovarian epithelial cells. The highest level of BRCA2-mutated allele transcript expression was measured in cells originating from the most aggressive ovarian tumor. The penetrance of the mutation and the aggressiveness of the related tumor could depend on a dosage effect of the mutated allele transcript.

paywalled: Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery (Lynch Syndrome, breast/ovarian BRCA 2....)

 Blogger's Note: while full access is by subscription only, key words indicate 'high risk' categories not limited to Lynch Syndrome, BRCA 2;  BRCA 2 - blogger's assumption based on genetics in absence of full text acccess)

Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery

Abstract 

Pancreatic cancer (PC) is a highly lethal disease. Despite advances regarding the safety and long-term results of pancreatectomies, early diagnosis remains the only hope for cure. This necessitates the implementation of an intensive screening program (based mainly on modern imaging), which – given the incidence of PC – is not cost effective for the general population. However, this screening program is recommended for individuals at high-risk for PC development.

Indications for screening include the following three clinical settings: hereditary cancer predisposition syndromes associated with PC, hereditary pancreatitis and familial pancreatic cancer syndrome. The aim of this strategy is to identify pre-invasive (precursor) lesions, which are curable. Surgery is recommended in the presence of recognizable lesion on imaging lesions. Partial (anatomic) pancreatectomy – depending on the location of the suspicious lesion – is the most widely accepted type of surgical intervention in this setting; occasionally, however, total pancreatectomy may be required, in carefully selected patients. Despite that experience still remains limited, there is evidence that this aggressive strategy allows early detection of neoplastic lesions, thereby improving the effectiveness of surgery and prognosis.

Keywords: Pancreas, Surgery, Cancer, PanIN, MCN, IPMN, Pancreatectomy, Total pancreatectomy, Screening

Abbreviations: PanIN, pancreatic intraepithelial neoplasia, IPMN, intraductal papillary mucinous neoplasm, MCN, mucinous cystic neoplasm, PJS, Peutz–Jeghers syndrome, FAMMM syndrome, familial atypical multiple mole melanoma syndrome, HNPCC, hereditary non-polyposis colon cancer (Lynch syndrome), HOBC, hereditary ovarian and breast cancer, VHL, von Hippel–Lindau, PD, pancreatoduodenectomy

Protein made by breast cancer gene purified - BRCA 2/RAD51

Objective To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation (abstract)

Objective

To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation.

Conclusion

The prevalence of tubal p53 signature and TIC (tubal intra-epithelial carcinoma)  increases with age at salpingectomy and with BMI. Oral contraceptive use is associated with a decrease in the prevalence of TICs.

Risk factors for carcinoma of the fallopian tube in women with and without a germline BRCA mutation

Reminder on stats: < 1.0 is decreased risk; > 1.0 is increased risk; OR=overall risk; edited some stats for ease of reading - see abstract/read more:

Conclusions

Parity and oral contraceptive use are associated with reduced risks of fallopian tube cancer. In contrast, hormone replacement therapy may be associated with an increase in the risk of fallopian tube cancer.

Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: A meta-analysis

CONCLUSIONS: OC users carrying an ascertained BRCA1/2 mutation have a reduced risk of ovarian cancer, proportional to the duration of use. There is no evidence that recent OC formulations increase breast cancer risk in carriers

Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts

BACKGROUND:
Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2.

CONCLUSIONS:
These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.

Teal Toes: Women’s Health Week, Ovarian Cancer media/video - link between breast/ovarian cancers

Note: no mention of other genetic risks aside from the BRCA's

Gene link to cancer risk in families - protein RAD51C (news item) breast and ovarian

Note: this report is worthwhile reading especially for those who test negative for BRCA 1/2

"No significant mutations were found in RAD51C in the 620 families with breast cancer only.  However, when they looked at the breast and ovarian cancer families, things got really interesting.  In all, they were able to identify a total of 6 mutations in the 480 families that had sufficient evidence to implicate them in the breast and ovarian cancer susceptibility.  Thus, in this German study of women with unexplained familial breast and ovarian cancer, the cancer susceptibility in 1.3% of the families could be explained by heterozygous mutations in the RAD51C gene."

Sleep disturbances in asymptomatic BRCA1/2 mutation carriers: women at high risk for breast-ovarian cancer

"Fatigue and carrier status were significant predictors of sleep quality, accounting for 15.7% of the variance.
In conclusion, asymptomatic BRCA1/2 carriers experience poor sleep quality compared to non-carriers and controls. Our study design is unique in that it offers insight regarding the nature of being an asymptomatic carrier, and affords the opportunity to examine factors that may contribute to the development of insomnia in women at risk for breast-ovarian cancer."

media article: The inherited malignancy of breast cancer (and ovarian cancer)

Note: good article, albeit complicated subject matter - excerpts of important information:

Genetic Alliance Weighs in On AMP's Desire to Outlaw Gene Patenting GenomeWeb

Molecular Cancer | Full text | Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas

full free access: Is no news good news? Inconclusive genetic test results in BRCA1 and BRCA2 from patients and professionals' perspectives

Small study but included view of patients and physician views.