Help needed on Germline HRR result

[dudubaya]

Hi All,

have attached fathers Germline HRR testing report we just received, much appreciate any help in interpreting the results, is there any indication for use of PARP inhibitors or otherwise ?

Thanks

[dudubaya]

+ remaining part of the report

test report

[dudubaya in reply to dudubaya]

Part 1

report

[dudubaya in reply to dudubaya]

part 2

report

[dudubaya in reply to dudubaya]

part3

report

[dudubaya in reply to dudubaya]

part 4

report

[dudubaya in reply to dudubaya]

part 5 final

report

[Mike58 in reply to dudubaya]

Copy and paste into ChatGPT and ask it to put into simple terms. Generally works a treat.

[dudubaya in reply to dudubaya]

Simplified report after running it through ChatGPT as suggested by Mike58 :-

Simplified Medical Report:

Diagnosis: Prostate Cancer

Genetic Testing Results:

A gene test found a 'likely pathogenic' variant in the BRCA2 gene.

This variant is associated with an increased risk of hereditary breast ovarian cancer syndrome (HBOC).

HBOC can lead to higher risks of breast and ovarian cancer for women and prostate, male breast, and pancreatic cancer for men.

Inheritance:

The identified variant is heterozygous, meaning it's present in one copy of the BRCA2 gene.

HBOC related to BRCA2 variants is inherited in an autosomal dominant manner.

First-degree relatives may have a 50% chance of having this variation if it's not a new (de novo) variant.

Recommendations:

Genetic counseling is advised to discuss the implications of this result.

Consult with your doctor for surveillance measures.

Consider genetic testing for the BRCA2 variant in adult family members.

Reanalysis of the data is recommended annually to stay updated on new genetic information.

Gene Background:

BRCA2 is a gene linked to hereditary breast cancer and is a tumor suppressor.

Variants in BRCA2 can increase the risk of breast, ovarian, and other related cancers.

The identified variant causes a frameshift and likely results in a non-functional protein.

Mutation Detail:

Gene: BRCA2

Specific Variant: chr13:32899243_32899246delGT, c.347_350delGTCT, p.Ser116IlefsTer4

Type: Heterozygous (Present in one copy of the gene)

Classification: Likely Pathogenic

Explanation:

Location: The mutation occurs in exon 4 of the BRCA2 gene.

Predicted Effect: This deletion leads to a frameshift, resulting in a premature stop signal in the gene sequence.

Protein Effect: The alteration leads to a truncated protein (p.Ser116IlefsTer4) that is much shorter than the normal protein.

Functional Impact: This change is likely to cause loss-of-function, meaning the protein may not function correctly.

NMD Mechanism: It is predicted that the altered protein may be targeted for degradation by the Nonsense-Mediated mRNA Decay (NMD) mechanism.

Not Previously Reported: This specific variant hasn’t been previously documented in medical literature.

Similar Pathogenic Variants: Other mutations in proximity (such as p.Leu117Serfs and p.Thr122Leufs) are associated with pathogenic effects related to hereditary breast ovarian cancer syndrome (HBOC).

[Tall_Allen]

Sorry, it is too small on my screen to read.

[dudubaya in reply to Tall_Allen]

Thanks TA for trying , I labored to get this into an image format will try to reattach again after making it larger, hopefully you can take another shot. Have been unable attach in PDF or doc format , is that even possible to attach pdfs directly to the post here?

[GP24]

The first page is difficult to read. You have a BRCA2 mutation and you should take Olaparib i.e. Lynparza.

[dudubaya in reply to GP24]

Thanks for trying , will reattach one with larger fonts shortly

[Tall_Allen]

If you like, you can send me a PM, and I can give you my email address.

[dudubaya in reply to Tall_Allen]

That would be great TA

[EdBar]

Check with his oncologist in order to get qualified advice.

Ed

[dudubaya in reply to EdBar]

Sure Edbar, thats a given and I have already shot him a mail , I try to run any reports through this forum so that I am prepared and ready with all my questions when we meet our MO/RO.... it has really helped me that way

[Har036]

It is difficult to read but looks like its a ATM and CHEK mutation?

My husband has both noted on his report too. His doctor was very hesitant to use Lynparza, (PARP) but we tried it. That was 37 months ago. He just had follow up scans which showed no progression or new lesions and his PSA is still undetectable. Prior to Lynparza he had Provenge and Zitiga/Prednisone that failed. He also completed Xofigo.

Praying that your father finds the best treatment option.

[MoonRocket in reply to Har036]

There a gray area for people with ATM and parps inhibitors. Some MOs now feel the original results of parps inhibitor trials involving ATM patients were schewd due to false positives ATM findings due to liquid biopsies. Up to 50% false positives. I'm glad your husband had positive results to lynparza.

[dudubaya in reply to Har036]

Thanks for going through it, high level summary says BRCA2 mutation which is "likely pathogenic". Rest of the report has some explanations regarding the location of the mutation and possible impact i suppose

[Har036]

BRACA 2 mutations have had positive results using PARP. How’s your father’s blood counts? PARP can adversely affect blood counts as well as QOL.

[dudubaya in reply to Har036]

Blood count is an area of concern as his Hgb is around 10 and RBC is around 4 , he has been on ADT for 2 years and this seems to be one of the SEs from it