17-year-old boy has multiple lung nodules, the genetic risk of lung cancer must be careful

Is lung cancer inherited? Everyone is very concerned about this issue
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Studies have found that some heritable germ cell mutations in the EGFR gene may indeed increase the risk of lung cancer
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What is the difference between germ cell mutation and somatic mutation? Let me explain to you the germ cell mutation and somatic mutation first
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Germ cell mutation: Almost all genetic mutations carried by human embryos are inherited from parents
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Since all human cells, including germ cells, carry such mutations, they can also be passed on to offspring
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Somatic mutation: The mutation that occurs in human cells during the acquired growth and development, such as gene mutation in tumor cells, this is only present in tumor cells, other normal cells do not, and will not be passed on to offspring
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Although the main risk factor for lung cancer is smoking, if a patient has germ cell mutations in the EGFR gene, such as T790M, V843I and P848L, these mutations may be passed on to the next generation, resulting in a higher susceptibility to lung cancer
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Family inherited EGFR gene R776H germ cell mutation, a 17-year-old boy with multiple lung nodules.
A 42-year-old woman without smoking history was admitted to the hospital because of discomfort.
CT examination found multiple lung nodules, most of which were ground glass nodules
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There is a 0.
94 cm X 0.
71 cm lesion in the middle lobe of the right lung
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On May 7, 2020, the patient underwent surgery
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Pathological examination showed invasive lung adenocarcinoma, and the pathological stage was stage 1A
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A genetic test was performed on the patient’s surgical samples, and it was found that there was a somatic mutation of EGFR gene G719A in lung cancer, but the patient’s embryonic cells also had a mutation of EGFR gene R776H
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Since the patient's pathological stage was 1A, no adjuvant treatment was given, but the most recent follow-up found signs of recurrence or metastasis
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The doctor then studied the patient’s family history and found that the patient’s father died of oral cancer, the patient’s mother died of lung cancer at the age of 65, and the patient’s mother’s younger brother also died of lung cancer
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Figure 1.
The patient has detected somatic and blast cell gene mutations.
Because the patient has a family history of lung cancer, the researchers sequenced the patient’s mother and son and found that the patient’s son had a EGFR gene R776H blast cell mutation, but the patient’s mother did not have this Mutation
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Figure 2.
Family diagram of lung cancer and gene mutation in the patient's immediate family members.
In June 2020, the patient's 17-year-old son found multiple ground glass nodules in both lungs during CT imaging examination
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Because the child was young, he had regular imaging examinations until the latest follow-up showed signs of disease progression
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The boy’s multiple pulmonary nodules are likely to be related to the blastoblast mutation at EGFR R776
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There are also previous case reports that the blast cell mutation at EGFR R776 can potentially affect the susceptibility to lung cancer: 1.
A mother and daughter from a white family were diagnosed with lung squamous cell carcinoma.
Their blast cell mutations all have the R776H mutation in the EGFR gene.
Tumor cells have G719A mutation and G719S mutation of EGFR gene respectively
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2.
A patient with a R776G mutation in the EGFR gene of blast cells.
This patient also has a L858R mutation in tumor cells.
The age of onset was only 47 years old
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How to use EGFR R776H mutation? EGFR R776H may also appear in tumor cells as a somatic mutation
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In non-small cell lung adenocarcinoma, the frequency of EGFR gene mutations is relatively high
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If there is a deletion mutation in exon 19 and an L858R point mutation in exon 21, the patient is more sensitive to targeted therapy
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However, many times, lung cancer patients have detected some rare gene mutation sites through second-generation sequencing.
The therapeutic drugs for these sites are often uncertain.
R776H is such a site
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On February 14, 2020, a 48-year-old male patient with no history of smoking was admitted to the hospital for examination
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During physical examination, a mass in the upper left lung was found, and CT imaging examination confirmed a tumor lesion measuring 4.
5 cm X 4.
4 cm
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There are multiple enlarged lymph nodes in the mediastinum and hilar lymph nodes
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PET-CT examination found multiple bone metastases, pathologically diagnosed as stage IVB
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The patient underwent a bronchoscopy biopsy and was pathologically diagnosed as lung adenocarcinoma
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After second-generation gene sequencing, the L861Q mutation and R776H mutation in exon 21 of the EGFR gene were discovered
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Subsequently, the F113V mutation of the TP53 gene was also discovered
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The detected EGFR gene mutation sites are all rare mutations
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The patient was treated with the second-generation targeted drug afatinib
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Take the medicine once a day, 40 mg each time
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The treatment effect of afatinib was very good.
The patient's tumor lesions shrank quickly and achieved partial remission within one month (tumor lesions shrank by more than 30%)
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Figure 3.
Imaging examination and gene mutation characteristics of the patient after treatment with afatinib.
After using afatinib for 8 months, the lung tumor lesions became 1.
9 cm x 1 cm, which was clinically assessed as resectable
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The patient underwent a left upper lobectomy and continued to be treated with afatinib after the operation, until the follow-up in March 2021, the condition was stable
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In addition, it has been reported in the literature that patients with EGFR gene L861Q and R776H mutations, using the first-generation targeted drug gefitinib, are in stable condition, but the progression-free survival period is only 2.
2 months
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In contrast to this case, if this rare EGFR mutation occurs, the second-generation targeted drug afatinib should be used
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Beware of genetic mutations in the EGFR gene.
What can we learn from these case reports? If it is a relatively young lung cancer patient who is found to have a blast cell mutation in the EGFR gene R776H during genetic testing, you need to be very careful
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In this case, the immediate family members should be prompted to perform genetic testing to verify whether they carry the mutation
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Although this mutation is not a mutation that directly drives tumors, it may indirectly promote the production of other mutations in the EGFR gene, which may lead to lung cancer
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Finally, the degree of cancer reminds patients to pay attention to the choice of targeted drugs.
If there are rare mutations in the EGFR gene, they should choose to use the second-generation targeted drugs afatinib or dacomitinib
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For more cancer prevention and treatment knowledge, welcome to download the cancer degree APP
.

Reference: Guo T, et al.
,Two cases of non-small cell lung cancer patients with somatic or germline EGFR R776H mutation, Lung Cancer (2021) Click below to learn more about clinical trial projects in the past.
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