Two Japanese families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A: a case report.

Background: Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) (OMIM #155,601), which is associated with an increased risk of pancreatic ductal adenocarcinoma and melanoma. FAMMM has been reported globally, but it is quite rare in Japan. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.

The response of pancreatic acinar cell carcinoma to platinum and olaparib therapy in a germline BRCA2 variant carrier: case report and literature review.

A 73-year-old Japanese man with a history of distal biliary cancer treated by pancreatoduodenectomy developed pancreatic acinar cell carcinoma (PACC) treated by remnant pancreatectomy and adjuvant chemotherapy. Thirteen months after surgery, multiple liver metastases developed and FOLFOX chemotherapy was initiated. Based on the PACC diagnosis and a positive family history for breast and ovarian cancer genetic testing was performed which revealed a pathogenic germline BRCA2 variant (c.

A Japanese Family Meeting the Clinical Diagnostic Criteria for MEN1 with a MEN1 Variant of Uncertain Significance.

Multiple gastroenteric, pancreatic, and pituitary neuroendocrine neoplasms (NENs) were diagnosed in a 74-year-old man with a history of primary hyperparathyroidism (PHPT). Germline testing demonstrated a variant of MEN1 (c.1694T>A, p.

Discordant microsatellite instability findings in two samples from a patient with biliary cancer that responded to pembrolizumab.

Microsatellite instability (MSI) is a key marker to predict response to immune checkpoint inhibitors; however, only 1-2% of biliary cancers have this genomic feature. In a patient with hilar biliary cancer, MSI was examined in two cancer specimens (forceps biopsy from the biliary stricture and endoscopic ultrasound-guided fine-needle aspiration biopsy [EUS-FNAB] from the adjacent lymph node). We observed discordant results, as high frequency of MSI was found only in the forceps biopsy.

A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2.

Germline double heterozygosity (GDH) is rarely reported in cases of inherited cancer syndromes, and GDH of a mismatch repair gene and BRCA has never been reported in Japan. Nonetheless, the current report demonstrates a case of ovarian mucinous adenocarcinoma with initiated Lynch syndrome (LS)-related surveillance because of a known germline MSH2 variant. Six and a half years after oophorectomy, multiple tumors developed in the patient's lungs, bones, and lymph nodes, and histology results confirmed mucinous adenocarcinoma.

A Cross-sectional Study of Regret in Cancer Patients After Sharing Test Results for Pathogenic Germline Variants of Hereditary Cancers With Relatives.

Background: Research on whole genome/exome sequencing is increasing worldwide. However, challenges are emerging in relation to receiving germline pathogenic variant results and sharing them with relatives.

Objective: The aim of this study was to investigate the occurrence of and reasoning related to regret among patients with cancer who shared single-gene testing results and whole exome sequencing with family members.

A Japanese case of familial malignant melanoma with germline CDK4 variant incidentally diagnosed by cancer genome profiling.

Familial malignant melanoma (FMM) is a hereditary tumor that is quite rare in Japan; to date, the germline CDK4 variant has scarcely been reported around the world. Thus, we report on a woman with FMM who developed salivary gland cancer, for which a germline pathogenic variant of CDK4 was incidentally identified through comprehensive genomic profiling. She had a history of multiple atypical nevi and a facial melanoma since her 30 s and multiple family histories of melanoma; however, none of her relatives were aware of its heredity.

Discordance of microsatellite instability and mismatch repair immunochemistry occurs depending on the cancer type.

Microsatellite instability (MSI) and deficiency of mismatch repair (dMMR) are key markers for predicting the response of immune checkpoint inhibitors (ICIs) and screening for Lynch syndrome (LS). This study examined the incidences of and factors associated with the concordance of MSI and MMR in human cancers. A total of 518 formalin-fixed cancer tissues were analyzed for MSI and MMR immunohistochemistry (IHC).

Present status of germline findings in precision medicine for Japanese cancer patients: issues in the current system.

Objective: Since 2019, precision cancer medicine has been covered by national insurance in Japan; however, to date, germline findings have not been fully reported. The aim of this study was to evaluate the current status and raise a problem of germline finding analysis and disclosure in Japanese precision cancer medicine.

Methods: Germline findings of 52 genes were examined in 296 cases with advanced cancer by a case series study.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

Background: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS).

Aim: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine.

Methods: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors.

Disclosure of secondary findings in exome sequencing of 2480 Japanese cancer patients.

High-throughput sequencing has greatly contributed to precision medicine. However, challenges remain in reporting secondary findings (SFs) of germline pathogenic variants and managing the affected patients. The aim of this study was to examine the incidence of SFs in Japanese cancer patients using whole exome sequencing (WES) and to understand patient preferences regarding SF disclosure.

Metachronous ovarian endometrioid carcinomas in a patient with a PTEN variant: case report of incidentally detected Cowden syndrome.

Background: Somatic PTEN mutation occurs in a proportion of ovarian endometrioid carcinomas. However, these cancers have seldom been reported in diseases associated with germline PTEN variants, such as Cowden syndrome (CS).

Case Presentation: The present case was a 39-year-old woman with a left ovarian carcinoma who demonstrated a germline splice variant of PTEN (c.

Germline mismatch repair gene variants analyzed by universal sequencing in Japanese cancer patients.

Background: Lynch syndrome (LS) is the commonest inherited cancer syndrome caused by pathogenic variants of germline DNA mismatch repair (g.MMR) genes. Genome-wide sequencing is now increasingly applied for tumor characterization, but not for g.

Renal Cell Carcinoma and a Pancreatic Neuroendocrine Tumor: A Coincidence or Instance of Von Hippel-Lindau Disease?

We herein report a rare case of a 79-year-old man who presented with the simultaneous occurrence of pancreatic neuroendocrine tumors (PNET) and renal cell carcinomas (RCC), without any other Von Hippel-Lindau (VHL)-associated lesions or any pertinent family history. Computed tomography showed vascular-rich solid lesions in the left kidney and the pancreatic tail, measuring 72 mm and 15 mm in size, respectively. Preoperatively, RCC with pancreatic metastasis was suspected and laparotomy was performed.

Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation.

A minor fraction of pancreatic ductal adenocarcinoma (PDAC) develops in association with germline mutations of the genes responsible for inherited cancer syndromes. However, the PDAC that has a germline PTEN mutation has not received much attention. Genome-wide whole exome sequencing was performed on germline and somatic DNA from an 82-year-old woman who had developed a solid pancreatic cancer but did not show characteristic findings of PTEN hamartoma tumor syndromes (PHTS).

Germline and somatic genetic changes in multicentric tumors obtained from a patient with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused by germline mutations of the gene located in chromosome 11q13. In patients with MEN1, multicentric tumors develop in the involved organs; however, precise evaluation of genetic changes in these multicentric tumors has not been performed. In the present study, using whole-exome sequencing, we analyzed germline and somatic genetic changes in blood cells, two pancreatic endocrine tumors and one duodenal tumor obtained from a patient with MEN1 gastrinoma.

A case of type 1 multiple endocrine neoplasia with esophageal stricture successfully treated with endoscopic balloon dilation and local steroid injection combined with surgical resection of gastrinomas.

Background: In type 1 multiple endocrine neoplasia (MEN1), esophageal diseases association with excessive gastrin secretion in Zollinger-Ellison syndrome (ZES) sometimes develop. Here, we reported a case of MEN1/ZES, who developed dysphagia due to reflux esophagitis with severe esophageal stricture. Treatment for his esophageal stricture and ZES was discussed.