Table 4.
Referral for history of multiple primary malignancies and/or family history of relatives with cancer at early ages
| Age/ Sex |
Cancer History | Family History | Somatic Mutation Testing |
Cytogenetics | Met Revised Chompret Criteria? |
Germline Mutation? |
|---|---|---|---|---|---|---|
| 58/M | Testicular seminoma age 10 months (tx surgery only) Papillary thyroid cancer age 44 tx RAI Essential thrombocytosis/MPN age 44 |
Son with astrocytoma age 5 Mother died age 63 of lung cancer Maternal aunt with bone cancer age 50 |
JAK2-V617F | 46,XY[20] | No | TP53 Negative |
| 46/F | Rectal cancer age 32 Cervical carcinoma in situ age 34 Bronchioalveolar carcinoma age 35 CML age 45 |
Father lung cancer age 68 Paternal grandmother with rectal cancer age 75 |
N/A | 46,XX,t(9;22)(q34;q11.2)[19] 46,idem,t(5;16)(q31;p13.1)[1] |
Yes | TP53 Negative MMR testing also negative |
| 48/M | Hodgkin Lymphoma age 15 s/p XRT CML age 29 s/p SCT Meningioma age 47 s/p resection Papillary and follicular thyroid cancer age 48 |
2 paternal uncles with unknown cancers in 50–60s | N/A | N/A | No | TP53 Negative |
| 68/F | Colorectal cancer age 52 s/p surgery and chemoXRT Osteosarcoma age 63 s/p surgery and chemotx Acute myeloid leukemia age 68 |
Unremarkable | TP53 c.507_530del p.M169_P177delin sI 68.3% allelic frequency |
43~46,XX,del(5)(q13q35),+6,+9,−10, der(11)dup(11)(q23q24) add(11)(q24)dup(11)(q23q24) add(11)(q24),der(11)t(5;11)(q13;p15)dup(11)(q23q24) add(11)(q24)dup(11)(q23q24)add(11)(q24),−13,der(13;17)(q10;q10), der(16)add(16)(p13.3)ins(?;11)(?;q23q24)x2add(11)(q24),+19,add(21)(p11.2),+1~2mar[cp18] |
No | TP53 Negative |
| 40/F | Astrocytoma age 12 s/p chemoXRT Neurofibroma thigh age 31 Brainstem gliosarcoma age 35 s/p chemoXRT Pre-B ALL age 37 |
Sister lymphoma age 32 Sister melanoma age 35 |
ALL sample: KRAS c.38G>A p.G13D Gliosarcoma: BRAF c.1799T>A p.V600E |
46,XX,add(8)(p21),−9,i(9)(q10),t(14;19)(q32;p13),+der(?)t(9:?)(p13;?)[18] | Yes | MLH1, MSH2, MSH6, PMS2, EPCAM, NF1, TP53 all negative |
| 25/M | T-cell ALL and synchronous low-grade astrocytoma age 24 | Daughter with rhabdomyosarcoma age 2 | TP53 c.524G>A p.R175H NOTCH1 c.4754T>C p.L1585P NOTCH1 c.7003dupC p.L2335fs*19 |
1~45,XY,−1,add(1)(p13),add(1)(p36.1),add (5)(q31),der(6)add(6)(p12)dup(6) (q23q23),+7,−12,−16,del(17)(p11.2),−19,+21,+1~2mar[cp13]/46,XY[7] |
Yes |
Germline TP53 p.R175H mutation *93.8% allelic frequency, presumed LOH |
| 71/F | DCIS age 57 s/p surgery and tamoxifen CLL age 66 Bilateral papillary thyroid cancer age 69 s/p RAI Pulmonary neuroendocrine tumor age 70 |
Brother with bronchioalveolar carcinoma age 66 Brother with testicular cancer age 64 Father with lung cancer, nonsmoker at 69 |
N/A | 46,XX[20] | No | TP53 and PTEN negative |
| 45/M | Rhabdomyosarcoma age 42 s/p adriamycin/ifosfamide × 6 cycles and 50 Gy XRT and surgery Acute Myeloid Leukemia age 44 |
Sister died at age 3 of cancer Father died at age 43 with cancer of unknown primary |
TP53 c.800G>A p.R267Q (59.2% allelic frequency) TP53 c.467G>A p.R156H (54.9% allelic frequency) TET2 c.4138C>T p.H1380Y |
44,XY,del(5)(q13),add(7)(q11.2), −11,−12,−17,−17,+r,+mar[18]/44,XY,del(5)(q13q33),add(7)(q11.2),−11,−12,−17,−17,+1~2mar[cp2]/ | Yes |
Both TP53 mutations identified in germline and clinically classified as VUS *clinical TP53 testing in his mother initiated for additional characterization of inheritance |
| 62/M | Liposarcoma age 24 s/p XRT and surgery Leiomyosarcoma R leg Myxoid malignant fibrous histiocytoma age 60 CLL/SLL age 60 |
Identical twin brother with CLL age 55 and leiomyosarcoma right leg age 58. Deceased age 61. Sister with DCIS age 49. Niece with melanoma age 12. Mother with breast cancer age 44, deceased age 46 |
N/A | N/A | TP53 negative | |
| 52/F | CLL age 44 | Brother with sarcoma age 20 Mother with breast cancer age 36 |
TP53 c.743 G>A p.R248Q (17.5% allelic frequency) | 46,XX[20] | TP53, BRCA1 and BRCA2 negative | |
| 28/F | Diploid AML diagnosed during pregnancy age 22 | Nephew with sarcoma age 14 | N/A | 46,XX[20] | TP53 testing negative | |
| 73/M | Gastric cancer age 45 s/p partial gastrectomy Prostate cancer age 68 s/p surgery Hodgkin Lymphoma age 70 s/p chemotx Marginal zone lymphoma age 72 s/p Rituxan Myelodysplastic syndrome age 73 |
One daughter with meningioma One brother with prostate cancer age 60 |
TP53 c.614A>G p.Y205C (21.2% allelic frequency) TET2 c.3765C>A p.Y1255* |
45,XY,add(2)(p12),−5,−7,t(11;17)(q13;p11.2),+mar[7]/46,XY[13] | Declined testing | |
| 57/M | CML diagnosed age 54 | Sister deceased breast cancer age 37 Maternal aunt with breast cancer age 70 |
BRCA1/2 and TP53 tumor testing negative | 46,XX,t(9;22)(q34;q11.2)[18]/46,XX[2] | TP53, BRCA1 and BRCA2 negative |