Tempus HRD

Question 1

What is HRR?

Answer 1

Homologous Recombination Repair

Question 2

What is it?

Answer 2

it’s a mechanism in our bodies that prevents cancer from happening.

Question 3

Proteins that are part of the HRR pathway recognize that a double-stranded DNA break has occurred and send out a signal. T or F?

Answer 3

True

Question 4

What are the steps here?

Answer 4

1. ) Other proteins in the HRR pathway assemble and create a repair complex
   2) The repair complex “recruits” the chromosome’s homolog and brings it over to serve as a template.
2. ) Using that template, the repair complex is able to rebuild the broken DNA strands of the original chromosome.

Question 5

HRD occurs when the HRR is not functioning properly, T or F?

Answer 5

True

Question 6

T or F, HRR pathway is highly complex and multiple genes and proteins are involved ?

Answer 6

True

Question 7

What genes are included in this?

Answer 7

BRCA1 and BRCA2

Question 8

Two-hit hypothesis

Answer 8

First hit and second

Question 9

First hit:

Answer 9

Germline or Somatic mutation in the HR gene

Question 10

Second hit:

Answer 10

Somatic mutation or other mechanisms inactivates the second copy, leads to “loss of heterozygosity” for that gene.

Question 11

HRD is observed in multiple cancer types. T or F?

Answer 11

True

Question 12

T or F, approx 50% of ovarian cancer is HR- deficient?

Answer 12

True

Question 13

HRD is also seen in what cancer types?

Answer 13

• Breast
• Prostate
• Pancreas

Question 14

HRD is a relatively common feature of cancer development, T or F?

Answer 14

True

Question 15

HRD occurs when ____ are not recognized and repaired by proteins in the HRR pathway

Answer 15

Double-stranded breaks

Question 16

T or F, loss of function of either BRCA1 or BRCA2 is a possible mechanism which leads to HRD?

Answer 16

True

Question 17

In which of these cancers is HRD NOT frequently observed?

Answer 17

Lung

Question 18

Can A “PARP” protein be the one to go in and repair damage?

Answer 18

Yes, this inhibitor can cause the cancer to die.

Question 19

PARP inhibitor therapy is somewhat limited by the FDA, T or F?

Answer 19

True. There has to be a gBRCAm, HRR gene mutation or BRCA mut.

Question 20

Tempus CANNOT claim any association to therapies including:

Answer 20

1) Eligibility for PARPi therapy
2) Response to PARPi therapy
3) platinum chemotherapy eligibility
4) platinum chemo treatment response

Question 21

Which statement about PARP inhibitors is “false”?

Answer 21

They are most effective in patients who do not have HRD

Question 22

The FDA has approved PARP inhibitors for:

Answer 22

• Breast cancers w/ germline BRCA mutations
• Prostate cancer w/ HRR mutations
• Pancreatic cancer w/ germline BRCA mutations
• Ovarian cancers regardless of HRR mutation status

Question 23

T or F, Tempus cannot claim any association with the Tempus HRD status with eligibility for or response to PARP inhibitors-

Answer 23

True

Question 24

What is the Tempus HRD test designed for?

Answer 24

to identify patients whose tumor has an HRD molecular phenotype.