bims-ovdlit 2022-05-15 papers

bims-ovdlit

Biomed News

on Ovarian cancer: early diagnosis, liquid biopsy and therapy

Issue of 2022–05–15
seven papers selected by
Lara Paracchini, Humanitas Research

Potential clinical utility of liquid biopsies in ovarian cancer.
TP53 variants in p53 signatures and the clonality of STICs in RRSO samples.
The interaction of p53 and DNA repair gene mutations and their impact on tumor mutation burden and immune response in human malignancies.
Tumour driver mutations compromise between cancer growth and immune responses.
Tools for the next generation.
Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy.
Fallopian Tube Originating Ovarian Cancer in a 53-Year-Old Postmenopausal Female With Hereditary Breast Cancer (BRCA) Genes: A Case Study.

Mol Cancer. 2022 May 11. 21(1): 114

Potential clinical utility of liquid biopsies in ovarian cancer.

Jie Wei Zhu, Parsa Charkhchi, Mohammad R Akbari.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. One of the main challenges in the management of OC is the late clinical presentation of disease that results in poor survival. Conventional tissue biopsy methods and serological biomarkers such as CA-125 have limited clinical applications. Liquid biopsy is a novel sampling method that analyzes distinctive tumour components released into the peripheral circulation, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free RNA (cfRNA), tumour-educated platelets (TEPs) and exosomes. Increasing evidence suggests that liquid biopsy could enhance the clinical management of OC by improving early diagnosis, predicting prognosis, detecting recurrence, and monitoring response to treatment. Capturing the unique tumour genetic landscape can also guide treatment decisions and the selection of appropriate targeted therapies. Key advantages of liquid biopsy include its non-invasive nature and feasibility, which allow for serial sampling and longitudinal monitoring of dynamic tumour changes over time. In this review, we outline the evidence for the clinical utility of each liquid biopsy component and review the advantages and current limitations of applying liquid biopsy in managing ovarian cancer. We also highlight future directions considering the current challenges and explore areas where more studies are warranted to elucidate its emerging clinical potential.

DOI: https://doi.org/10.1186/s12943-022-01588-8
J Gynecol Oncol. 2022 Mar 21.

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples.

Tomoko Akahane, Kenta Masuda, Akira Hirasawa, Yusuke Kobayashi, Arisa Ueki, Miho Kawaida, Kumiko Misu, Kohei Nakamura, Shimpei Nagai, Tatsuyuki Chiyoda, Wataru Yamagami, Shigenori Hayashi, Fumio Kataoka, Kouji Banno, Kokichi Sugano, Hajime Okita, Kenjiro Kosaki, Hiroshi Nishihara, Daisuke Aoki.

   OBJECTIVE: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.
METHODS: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.
RESULTS: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.
CONCLUSION: The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

Keywords:  Carcinoma in Situ; Cystadenocarcinoma, Serous; Genes, BRCA1; Genes, BRCA2; Genes, p53; Prophylactic Surgical Procedures; Salpingo-Oophorectomy

DOI:  https://doi.org/10.3802/jgo.2022.33.e50
Am J Cancer Res. 2022 ;12(4): 1866-1883

The interaction of p53 and DNA repair gene mutations and their impact on tumor mutation burden and immune response in human malignancies.

Xuemin Xue, Lin Dong, Edwina Burke, Liyan Xue, Yong-Jie Lu.

P53 suppresses tumorigenesis through multiple cellular functions/mechanisms, including genomic stability surveillance. Recently, it has also be reported for its role in cancer immune response modulation. Deficiency in DNA repair pathways lead to the accumulation of genomic alterations and tumor mutation burden and in consequence resulting in the activation of immune response. We investigated the interaction of p53 and DNA repair gene mutations and their impact on tumor mutation burden and immune response in human malignancies by mining cBioPortal data of a range of human cancers. We found that in the majority of human cancers, p53 mutations are equally distributed between DNA repair gene mutation positive and negative cases and in a number of human cancers, p53 and DNA repair gene mutations have a tendency of co-occurrence. Only in colorectal cancer, there is a tendency of 'mutual exclusivity' of mutations in p53 and DNA repair genes. In most tumors, p53 and DNA repair gene mutations have synergistic/additive effect in increasing tumor mutation burden, but not in colorectal cancer where they are mutually exclusive. The impact of p53 and DNA repair gene mutations and their interaction on tumor microenvironment immune cells are complex and tumor type specific and not always correlated with tumor mutation burden. In colorectal cancers, these two types of mutations resulted in similar immune cell subpopulation changes and in tumors where the mutations have a tendency of co-occurrence, p53 showed dominant roles on immune response, although they can also counter-act each other for their effect on certain immune cell subtypes.

Keywords: DNA repair gene; Gene mutation; P53; tumor infiltrating immune cell population; tumor mutation burden
Nature. 2022 May 11.

Tumour driver mutations compromise between cancer growth and immune responses.



Keywords:  Cancer; Cell biology; Immunology

DOI:  https://doi.org/10.1038/d41586-022-01138-8
Nat Rev Cancer. 2022 May 10.

Tools for the next generation.

DOI: https://doi.org/10.1038/s41568-022-00484-z
J Gynecol Oncol. 2022 Mar 31.

Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy.

Registration Committee of the Japanese Organization of Hereditary Breast and Ovarian Cancer

   OBJECTIVE: BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers.
METHODS: We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (gBRCA1m), germline BRCA2 mutation (gBRCA2m) and germline BRCA wild-type (gBRCAwt) were found in 185, 42 and 241 OC patients, respectively.
RESULTS: The average age at diagnosis of OC in gBRCA1m and gBRCA2m was 51.3 and 58.3 years, respectively, and the difference from gBRCAwt (53.8 years) was significant. The gBRCA2m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1, and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCA2. The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA2 carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40.
CONCLUSION: There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed.

Keywords:  Age at Diagnosis; BRCA1; BRCA2; Common Mutation; Ovarian Neoplasms; Risk-Reducing Salpingo-Oophorectomy

DOI:  https://doi.org/10.3802/jgo.2022.33.e46
Cureus. 2022 Apr;14(4): e23929

Fallopian Tube Originating Ovarian Cancer in a 53-Year-Old Postmenopausal Female With Hereditary Breast Cancer (BRCA) Genes: A Case Study.

Iana Garrick, Habiba Ahasan, Matthew Jiang, Yakubmiyer Musheyev, Farage Ftiha, Maria Levada.

  Ovarian cancer is the second most common gynecologic malignancy, but it is the deadliest of the gynecologic cancers. Out of 21,410 new cases of ovarian cancer in the United States in 2021, more than half were fatal. In this case study, a 53-year-old sexually active postmenopausal patient with a family history of breast cancer presented to her gynecologist for an annual exam. Given the patient's family history and breast cancer mutations, malignancy was a concern that had to be addressed. Elective bilateral salpingo-oophorectomy of the patient revealed ovarian serous carcinoma originating from the fallopian tubes. Historically, fallopian tube carcinoma was presumed to be rare, though many high-grade serous carcinomas previously classified as advanced ovarian carcinomas are now believed to have actually originated from the fallopian tubes. This case study adds to the body of evidence that many high-grade carcinomas have fallopian tube origins. This emerging perspective of ovarian cancer's origin provides healthcare workers and the scientific community a more complete picture of the etiologies and dissemination pattern of ovarian cancer. We hope this study will help physicians have a more extensive knowledge base of such a disease when looking for risk factors and taking care of their patients.

Keywords:  bilateral salpingo-oophorectomy; brca; fallopian tube; ovarian cancer; postmenopausal; serous carcinoma

DOI:  https://doi.org/10.7759/cureus.23929