A Novel Germline Mutation inBRCA1Causes Exon 20 Skipping in a Korean Family with a History of Breast Cancer

21029 Background: A specific germline mutation at codon 337 in TP53 (R337H) has been detected in a number of unrelated subjects with familial cancer risk in South Brazil, suggesting that this mutation may be relatively common in this population. Methods: To assess the TP53 R337H prevalence in a group of asymptomatic individuals unselected for family history of cancer, we studied 750 women aged 40–69 ys participating in a mammographic screening programme in Porto Alegre, Brazil`s southernmost capital. DNA was extracted from peripheral blood using standard procedures and PCR-amplified to generate a 238-base product encompassing TP53 exon 10, which was analyzed by RFLP using the restriction enzyme HhaI. The mutant, uncleaved allele was identified in agarose gels and positive RFLP findings were further confirmed by an independent PCR amplification and bi-directional, automated sequencing. Results and Discussion: The R337H mutant was detected in two of the 750 participants (0.15%), suggesting a much higher prevalence for this than for other TP53 germline mutations causing the LFS/LFL syndromes in the general population. Interestingly, these two subjects reported a familial history of cancer, and were found to be 2nd degree relatives. Three additional family members were also positive: one woman affected with breast cancer at the age of 36 years and two asymptomatic 62- and 80-year-old women. The presence of four R337H-positive cancer- unaffected individuals in this family, two of them well above the age of 50, indicates that this is a low-penetrance allele. In addition, the pedigree does not fulfill any of the currently recognized clinical criteria for the diagnosis of LFS/LFLS syndrome. This is the first study to report detection of a germline TP53 mutation in a population-based screening programme. Conclusions: The TP53 R337H mutant appears to be relatively common and may occur in families that do not fulfill the known clinical criteria for LFS/LFLS, the family described here contains asymptomatic carriers suggesting partial penetrance. No significant financial relationships to disclose.

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Mutation screening of germline TP53 mutations in high-risk Chinese breast cancer patients

BMC Cancer ◽

10.1186/s12885-020-07476-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Ava Kwong ◽

Vivian Yvonne Shin ◽

Cecilia Y. S. Ho ◽

Chun Hang Au ◽

Thomas P. Slavin ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Cancer Patients ◽

Germline Mutation ◽

Early Onset ◽

Mutation Screening ◽

Germline Mutations ◽

Breast Cancer Patients ◽

History Of ◽

History Of Cancer

Abstract Background Germline TP53 mutations are associated with Li-Fraumeni syndrome, a severe and rare hereditary cancer syndrome. Despite the rarity of germline TP53 mutations, the clinical implication for mutation carriers and their families is significant. The risk management of TP53 germline mutation carriers is more stringent than BRCA carriers, and radiotherapy should be avoided when possible. Methods TP53 gene mutation screening was performed in 2538 Chinese breast cancer patients who tested negative for BRCA mutations. Results Twenty TP53 mutations were identified with high next-generation sequencing concerning for germline mutations in Chinese breast cancer families. The majorities of the TP53 carriers had early-onset, hormone receptor-positive breast cancer, and had strong family history of cancer. Among all, 11 patients carried a germline mutation and 6 of which were likely de novo germline mutations. In addition, 1 case was suspected to be induced by chemotherapy or radiation, as this patient had no significant family history of cancer and aberrant clonal expansion can commonly include TP53 mutations. Furthermore, we have identified one mosaic LFS case. Two novel mutations (c.524_547dup and c.529_546del) were identified in patients with early-onset. Conclusions In view of the high lifetime risk of malignancy, identification of patients with germline TP53 mutations are important for clinicians to aid in accurate risk assessment and offer surveillance for patients and their families.

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Metastatic Lobular Breast Cancer Mimicking Colitis

Reports ◽

10.3390/reports3030020 ◽

2020 ◽

Vol 3 (3) ◽

pp. 20

Author(s):

Renata Reis Figueiredo ◽

Tatiana Strava Correa ◽

Carlos Henrique dos Anjos ◽

Heinrich Bender Kohnert Seidler

Keyword(s):

Breast Cancer ◽

Germline Mutation ◽

Lobular Carcinoma ◽

Progesterone Receptors ◽

Pathological Examination ◽

Lobular Breast Cancer ◽

Paternal Uncle ◽

History Of ◽

Lobular Breast Carcinoma ◽

Invasive Breast Carcinomas

Breast cancer is the most frequent cancer diagnosed in women in the world regardless of race or ethnicity. About 10% of invasive breast carcinomas are lobular subtype. The loss of the E-caderin expression that occurs in lobular carcinoma leads to a higher risk of metastases in membranes (meningeal, pleural, peritoneum) and gastrointestinal and/or endobronchial mucous, which may lead to several odd symptomatology. We report a 79 years old female patient with lobular breast cancer associated to CDH1 germline mutation. She was diagnosed with breast cancer in December 2016 after noticing a right-armpit nodule whose pathological examination demonstrated an immunohistochemistry profile compatible with lobular breast carcinoma metastasis and had estrogen receptors 98%, progesterone receptors < 1%, ki67 25%, negative her2 score. Family history of only one paternal uncle with stomach cancer. After two lines of hormone therapy, she had disease progression and started oral chemotherapy with capecitabine. In a few weeks, the patient had refractory diarrhea. At the beginning, it was defined like colitis chemotherapy related. However, the clinical features showed necessity of further investigation. Then, she was diagnosed with CDH1 germline mutation after massive progression at gastrointestinal mucous. This case made possible to inform the family about risk of germline mutation and necessity of genetic counseling.

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