Table 2. [Other Genes of Interest in the Differential Diagnosis of Li-Fraumeni Syndrome]. - GeneReviews®

Gene(s)	Disorder	MOI	Core Cancer(s)	Age at Cancer Onset	Comments
BRCA1 BRCA2	BRCA1- and BRCA2-associated hereditary breast and ovarian cancer	AD	Breast; ovary; pancreas; prostate; melanoma	Typically in adulthood	A BRCA1 or BRCA2 pathogenic variant is more likely in individuals w/: Premenopausal breast cancer, especially ER/PR/HER2-negative tumors Personal or family history of ovarian, pancreatic, male breast, or prostate cancer Ashkenazi Jewish ancestry No family history of adrenocortical carcinomas, CNS tumors, osteosarcomas, or soft-tissue sarcomas
CHEK2	CHEK2 cancer susceptibility (OMIM 609265)	AD	Breast; colorectal; prostate	Typically in adulthood	CHEK2 pathogenic variants are more likely to explain personal & family histories of predominantly breast, colon, prostate, or other adult-onset cancers.
MLH1 MSH2 MSH6 PMS2	Constitutional mismatch repair deficiency (a variant of Lynch syndrome)	AR	Colorectal; small bowel; hematologic; brain	Early childhood	CMMRD should be considered in individuals w/childhood-onset gastrointestinal cancer or polyps, malignant brain tumor, hematologic cancer, &/or café au lait macules.

Gene(s)

Disorder

MOI

Core Cancer(s)

Age at Cancer Onset

Comments

BRCA1
BRCA2

BRCA1- and BRCA2-associated hereditary breast and ovarian cancer

Breast; ovary; pancreas; prostate; melanoma

Typically in adulthood

A BRCA1 or BRCA2 pathogenic variant is more likely in individuals w/:

Premenopausal breast cancer, especially ER/PR/HER2-negative tumors
Personal or family history of ovarian, pancreatic, male breast, or prostate cancer
Ashkenazi Jewish ancestry
No family history of adrenocortical carcinomas, CNS tumors, osteosarcomas, or soft-tissue sarcomas

CHEK2

CHEK2 cancer susceptibility (OMIM 609265)

Breast; colorectal; prostate

Typically in adulthood

CHEK2 pathogenic variants are more likely to explain personal & family histories of predominantly breast, colon, prostate, or other adult-onset cancers.

MLH1
MSH2
MSH6
PMS2

Constitutional mismatch repair deficiency (a variant of Lynch syndrome)

Colorectal; small bowel; hematologic; brain

Early childhood

CMMRD should be considered in individuals w/childhood-onset gastrointestinal cancer or polyps, malignant brain tumor, hematologic cancer, &/or café au lait macules.

From: Li-Fraumeni Syndrome

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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