Can EGFR gene mutations also be inherited? How are patients with this lung cancer treated?

Genetic mutations are divided into germ cell mutations and somatic cell mutations, and germ cell mutations are congenital genetic mutations brought about by heredity; Somatic mutations are acquired mutations that are mostly caused
by environmental factors.
The EGFR gene in lung cancer belongs to the cancer driver gene, and the general EGFR gene mutation is a somatic mutation
.

So, is it possible that there is a germ cell mutation in the EGFR gene? This is rare, but it still exists
.
The researchers found that acquired somatic EGFR gene mutations are suitable for treatment with targeted drugs, and the effect of immunotherapy with PD-1 inhibitors is not ideal
.
Patients with germ cell EGFR gene mutations can benefit from PD-1 inhibitor therapy, let's take a look at the following cases
.

Congenital EGFR mutations, long-term benefit from the use of PD-1 inhibitors

A 61-year-old woman with a history of smoking was diagnosed with low-differentiation non-small cell lung cancer with metastatic lesions
found in the bone, adrenal glands, and liver.

Through the next-generation gene sequencing of the patient's tumor tissue sample, it was found that the patient had a relatively complex gene mutation
.
Specifically, there are G13D mutations in the KRAS gene, E17K mutations in the AKT1 gene, and V843I mutations in the EGFR gene, with a mutation frequency of up to 49%.

In general, different tumor driver gene mutations are unlikely to occur at the same time, because generally one is enough to drive cancer, so it is unlikely that the KRAS gene and the EGFR gene will appear at the same time, especially in patients who
have not yet been treated.

G13D of the KRAS gene is a relatively common mutation, and 8.
5% of the KRAS mutations in lung cancer are G13D site mutations
.
But V843I mutations in the EGFR gene are less common
.
This mutation may be a susceptible mutation that leads to predisposition to lung cancer, especially the 49% mutation abundance, and such a high mutation frequency suggests that it may be a germ cell mutation, because somatic mutations rarely have such a high mutation abundance
.
Later sequencing of the patient's white blood cells also confirmed that the V843I mutation in the EGFR gene was a germ cell mutation
.

So, can this mutation benefit from targeted drug therapy? There are no relevant reports for the time being, and there is no targeted drug
at the G13D site of the patient's KRAS gene.
Since the PD-L1 expression in the patient's cancer cells is 50%, which is a high expression, therefore, the patient directly uses PD-1 inhibitors
.

Figure: CT scan shows that immunotherapy has significantly reduced the tumor lesion

As shown in the figure above, the treatment effect is amazing
.
All visible tumor lesions are significantly reduced, manifested by a sustained response, and clinically assessed as partial remission
.
After 30 months of use of PD-1 inhibitors, the patient was found to have progressed in the location of previous metastases and second-line therapy
with pemetrexed plus carboplatin was started.
By June 2022, patients have reached 48 months or 4 years
.

revelation

The genetic testing information of the patient in this case indicates that the V843I mutation abundance of the EGFR gene reached 49%, which the researchers assessed as a germ cell gene mutation, because the gene mutation abundance of somatic cells rarely reaches such a value
.

The driver gene of the patient's tumor is the KRAS gene, not the EGFR gene, so it is logical to benefit from PD-1 inhibitor therapy
.
Whether other therapeutic measures can be interspersed in the middle of treatment to help prolong resistance to PD-1 inhibitors will need further research to confirm
.

Today's gene sequencing technology is constantly improving, but the overall level is mixed
.
The abundance of gene mutations detected by patients using tissue samples can reach 88%, that is, 88% of the tissue samples are cancer cells
.
There are also patients who use blood samples to detect a 40% abundance of gene mutations, or three driver gene mutations at the same time: EGFR, ALK, and RET, and the probability of these conditions is very low, so the credibility of this part of the genetic test report is worth considering
.

For patients with doubtful genetic test results, they can consult with professionals or cancer medical consultants, and attach importance to the verification of genetic test reports, so that this emerging diagnosis and treatment technology can truly become a credential
to guide the use of drugs for later treatment.

Cancer, accompany you through every step of the fight against cancer!

Reference: O.
Trabelsi Grati, L.
et al.
, Long response to Immune Checkpoint Inhibitors in metastatic NSCLC despite EGFR germline mutation.
A Case Report, Lung Cancer (2022)

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